EATG http://www.eatg.org European AIDS Treatment Group Thu, 23 Nov 2017 01:13:37 +0000 en-US hourly 1 https://wordpress.org/?v=4.8 MEP gets HIV test, calls for focus on key populations, including MSM and trans people http://www.eatg.org/news/mep-gets-hiv-test-calls-for-focus-on-key-populations-including-msm-and-trans-people/ Wed, 22 Nov 2017 22:59:17 +0000 http://www.eatg.org/?post_type=news&p=6824 This morning, Co-President of the LGBTI Intergroup Daniele Viotti MEP got an HIV test in the framework of the European HIV/hepatitis testing week.

The week has officially been endorsed by the European Commission and the European Parliament intergroup on LGBTI Rights.

Daniele Viotti MEP reacted: “HIV/AIDS is still a major public health concern, even though we have the science and the experience to end it as a threat. This is why I am calling for strong and sustained political engagement of the Commission to support evidence-based interventions at national level in order to get people diagnosed and linked to care early, and to access relevant prevention tools to reduce new infections.”

“Particularly, we need to increase HIV testing amongst the groups most affected by the epidemic, including homo- & bisexual men, other men who have sex with men (MSM), transgender people and other groups.”

Pierre Mayeur, President of Ex Aequo, the Belgium based gay organisation offering the free test in the Parliament, commented: “HIV testing should be key in the public response to the HIV/AIDS epidemic. The sooner a person knows their status, the sooner they will be treated and they will be less at risk of transmitting the virus since an HIV positive person following a treatment can no longer transmit the virus. Many local LGBTI organisations across Europe offer such services.”

“Talking to a general practitioner about sexual health remains difficult these days for most MSM. LGBTI NGOs are often the closest and most natural partner to talk to and people know they will not be judged nor frowned upon.”

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European Cure Review concentrates on HIV therapeutic vaccines http://www.eatg.org/news/european-cure-review-concentrates-on-hiv-therapeutic-vaccines/ Wed, 22 Nov 2017 22:55:36 +0000 http://www.eatg.org/?post_type=news&p=6815

A cure for HIV would almost inevitably have to involve a vaccine to improve the body’s natural ability to control HIV, a seminar on European HIV cure research heard recently. The STEPS seminar, held by the European AIDS Treatment Group (EATG) ahead of the 16th European AIDS Conference (EACS) in Milan last month, also heard that, in the words of Giulio Maria Corbelli, EATG member and European Community Advisory Board chair, “Cure research reminds us of the importance of patient involvement from the very earliest phases of the development of treatment and prevention.”

The cure: an elusive goal

Giulia Marchetti of the University of Milan opened the seminar with a general introduction to HIV vaccines, and particularly therapeutic ones.

She drew attention to an uncomfortable paradox in HIV cure. On the one hand, there are cases like the “Mississippi Baby” and the “Boston patients”, where someone is treated within hours of infection, or where cancer patients had what appeared to be their entire immune system replaced. In these cases, despite repeated assays failing to find even the slightest trace of HIV DNA buried inside cells, the virus came back from somewhere.

And yet we have the case of Timothy Ray Brown, now a decade into what appears to be a cure. We have elite controllers, who seem to be able to control their HIV viral load spontaneously, and we have “post-treatment controllers” such as those in the VISCONTI cohort and ones reported from Germany and France, that suggest that some people who receive early treatment may later be able to spend prolonged periods off treatment. These have been spontaneous cases, and we don’t as yet know why this happens to some people and not others.

In terms of attempting to deliberately induce viral control off therapy, we have been able to prolong the period a handful of patients can stay off therapy without viral rebound in one therapeutic vaccine trial, though others have been disappointing, and we have tantalising early results from vaccines and drugs in animal trials and in the test tube that indicate drug-free viral suppression for long periods, and even complete cure, may be possible.

Correlates of efficacy – how do we know what will work?

It is, however, still almost impossible to predict in advance what approach may work. Dr Felipe Garcia of the University of Barcelona Hospital is also one of the collaborating researchers in the European HIV Vaccine Alliance.

He told the seminar: “The problem with HIV vaccines is that what protects is not able to control and what controls is not able to protect.”

What he meant was that on the one hand, so-called broadly neutralising antibodies and vaccines that generate them – B-cell vaccines – may be able to completely block onward infection of cells by HIV, but tend to lose efficacy quickly as HIV is usually able to mutate enough to develop resistance to them, though one, PRO 140, has produced sustained viral load suppression for over a year. Experiments with combinations of ready-made broadly neutralising antibodies, including ones of novel design, showed more efficacy in human and monkey studies, but these were still passively introduced antibodies, used like drugs: the challenge was to produce a vaccine that could induce the body to make them.

Vaccines that stimulate the cellular immune response of cells to HIV – T-cell vaccines – could potentially generate a much longer-lasting immune response to HIV, but so far that response has been too weak and too narrow, at least in human studies, to produce more than a slight reduction in viral load, typically a threefold to tenfold (0.5 to one log) reduction in the size of the ‘reservoir’ of HIV-infected cells. A trial in monkeys produced much more sustained viral load reductions to the extent of producing an apparent cure in about half of them, but this vaccine may be tricky to adapt to humans.

Garcia quoted one mathematical model that suggested that an immune response would have to produce an ongoing ten thousand-fold drop in infected cells (4 logs) in order to produce lifelong remission.

He added that a more fundamental problem in vaccine trial design was that we still had no real correlates of immunity. Assays that have predicted efficacy in other vaccines in the past – such as the amount of interferon-gamma produced by cells – fail to do so for HIV vaccines. “After an immune response is validated by a trial,” said Garcia, “then I can tell you it’s a surrogate.”

Correlates of efficacy or immunity emerged from large-scale clinical trials, he said. But the problem in vaccines was that trials were very expensive – the RV144 trial, the only phase III study to find efficacy so far, had involved 16,000 participants and had cost €100 million. Multiple trials were needed to find an effective HIV vaccine, and it is estimated that over 35,000 volunteers will be required per year for phase I–III HIV vaccine trials worldwide to achieve this goal.

A better way is needed to select novel vaccine candidates for development, he said, and therapeutic vaccinations offered a way as trials of them did not need too many people. Even so, in a previous trial in which he had been involved, RISVAC02, 3056 volunteers had been screened to find 41 eligible candidates of whom 30 had eventually been enrolled.

Finally, because of the lack of surrogates, at present vaccine trials must assay and analyse a vast array of different proteins in case one of them turns out to be the crucial surrogate of efficacy. In a dendritic-cell vaccine trial Garcia was the principal investigator for, the activity of over 50,000 molecules was evaluated.

Combining approaches

This all added up to a formidable task for vaccine researchers. However, by combining approaches, the chances of generating a ‘hit’ when it came to a truly effective immune response were increased.

Strategies recently had included the following:

  • Latency-reversing agents such as PD-1 antagonists that prolonged the natural immune response to HIV and stopped the body ‘locking away’ HIV in the cellular reservoir.
  • HIV Conserv vaccines that focused on generating immune responses to the particular parts of the virus it could least afford to change and discarded less-relevant responses.
  • Combining vaccines with cytokines: these are specific cell-signalling molecules such as IL-15 and CXCR5 which are able to ferry vaccines and drugs into ‘sanctuary sites’ such as the lymph node follicles where HIV is normally able to replicate in cells that are shielded from immune-system surveillance.
  • Dendritic-cell vaccines.

Garcia had taken a particular interest in the latter. He explained: “Dendritic cells are the first line of defence in infection. They capture foreign molecules and present them to immune system cells as antigens. You need to target dendritic cells because if these cells don’t say to the body ‘you are infected’, the body doesn’t know it.

“The problem with HIV is that it has developed a loop in its membrane that allows whole live viruses to attach to the dendritic cell which then ferries them to the lymph nodes as a ‘Trojan Horse’. But this does mean that if we develop a vaccine that attaches to dendritic cells, it could generate a strong cellular immune response in the lymph nodes, which is where it needs to be.”

The European HIV Vaccine Alliance is a consortium of 39 partners from eleven countries in Europe plus four in sub-Saharan Africa and the US. It is pursuing a number of different preventative vaccine strategies including improved viral vectors, modified versions of HIV envelope proteins and dendritic-cell vaccines.

Garcia is also a lead investigator in the 14-site HIVACAR consortium. This involves three different therapeutic vaccine strategies that will be used in HIV-positive people separately and in combination. Firstly, vaccine antigens will be developed that are targeted not only at the conserved parts of the virus (iHIVARNA) but also designed with individuals’ own HIV virus’s gene profile in mind – (HIVACAR – truly individualised vaccines). Secondly, the vaccines will be followed by injections of broadly neutralising antibodies. Thirdly, messenger-RNA molecules (already used as experimental cancer drugs) will be injected after the HIV antigens and antibodies. These will be used to sensitise dendritic cells to the HIV antigens and further stimulate an immune response that will – it is hoped – kill off the HIV-infected cells in sanctuary sites that other strategies have failed to do.

And these vaccine components will all be given intranodally – that is, injected into individual lymph nodes – in the hope that taking the vaccine right to the site of HIV integration and replication will kick-start a stronger immune response to HIV that, it is hoped, will dampen down HIV replication to the point where individuals can be taken off antiretroviral therapy.

The HIVACAR protocols are in phase I/II trials – that is, evaluated for safety and immunogenicity – and then the most promising strategies will be taken forward into dosing trials – with results expected in 2021.

Other approaches

The Cure symposium also heard from the RIVER trial, part of the UK-based CHERUB consortium. This study is combining initial inoculations with vector-based vaccines with subsequent doses of the drugs called HDAC inhibitors to see if the two strategies together work better together. HDAC inhibitors, which reawaken the quiescent HIV reservoir cells, were among the first drugs tried as HIV cure agents but while they did reverse viral latency, they did not produce a useful diminution in the size of the viral reservoir. It is hoped that by priming the immune system to recognise the virus that is produced by the ‘woken’ reservoir cells, this diminution will be achieved. RIVER involves 50 volunteers in six sites in England and is due to announce results next year.

The symposium also heard an update on the ICISTEM cohort of cancer patients who have been given bone-marrow transplants (the cure approach similar to that given to Timothy Ray Brown and the Boston patients) but this has largely been reported in our summary of the HIV Cure symposium at the IAS conference in July this year.

Involving the community

Finally, as Felipe Garcia told the symposium, no HIV cure research is complete unless it also involves community collaboration and research into the psychosocial impact of cure studies.

“Any innovative therapeutic approach in HIV infection has ethical, economic, and psychosocial consequences,” he said.

“In HIVACAR, a detailed study about these aspects will be conducted, involving both participants in the clinical trial and the greater community of people living with HIV. Results will be disseminated to people living with HIV, policy makers and the general public in Europe to better inform their future decisions.”

Fred Verdult is a person living with HIV in the Netherlands who has used his experience in advertising and marketing to conduct a number of community opinion surveys and publicity events for HIV cure research and its potential.

He presented the results of one survey that showed that 72% of a group of 457 people with HIV felt it would be “very important” to them personally if there was a cure for HIV and only 6% thought it would not be important. When asked what was the biggest disadvantage of living with HIV, by far the most widely cited (by 91%) was the risk of possible adverse health effects in the future – either side-effects due to long-term antiretroviral therapy, or health problems due to chronic infection. Fewer people cited actual adverse effects happening right now but they were still a consideration for a majority (66%), as was the risk of, or anxiety about, infecting someone (also 66%).

Verdult said that the question of when to interrupt treatment remained a major ethical problem in HIV cure research – a dilemma already being pondered by ICISTEM. But there was also the inequalities involved. Ethically, if there had to be a choice of which people should benefit first from an HIV cure, it should logically be chronically infected people who had suffered most for years with immune suppression and suboptimal HIV therapy (“First in, first out”). However, these were likely to be the most difficult people to cure, so, with the exception of cancer patients, cure research had largely concentrated on the most recently infected people with intact immune systems (“Last in, first out”). Was this fair, he asked.

Finally, there is the issue that treatment as prevention and pre-exposure prophylaxis (PrEP) might be at the point of succeeding in producing large reductions in HIV incidence worldwide. If it did, scientific and funders’ interest in cure research might slacken. He urged a step-up in the pace of cure research now, so as not to lose a “window of opportunity”.

By Gus Cairns

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Despite reassuring data, we can’t yet say U=U for breastfeeding http://www.eatg.org/news/despite-reassuring-data-we-cant-yet-say-uu-for-breastfeeding/ Wed, 22 Nov 2017 22:50:33 +0000 http://www.eatg.org/?post_type=news&p=6820 Clinicians in high-income countries should take a harm reduction advice approach with HIV-positive mothers who breastfeed

While effective HIV treatment greatly reduces the risk of onward transmission during breastfeeding, it does not appear that the risk is zero, a leading paediatrician told the British HIV Association (BHIVA) conference in London last week. Although formula feeding is the safest option in high-income countries, some women will choose to breast feed and healthcare professionals should support them to do so as safely as possible.

Dr Hermione Lyall of St Mary’s Hospital, London said that she and colleagues often needed to advise patients who were doing well on HIV treatment, with an undetectable viral load, who wished to breastfeed. Many are aware of World Health Organization (WHO) guidelines which recommend breastfeeding for women with HIV. Many women say that breastfeeding is expected by their families and that they also believe it is the right thing to do.

However WHO guidelines are primarily written for countries with a high HIV prevalence where the lack of access to clean water means that the risk of HIV transmission through breastmilk must be weighed against the risks of infant malnutrition, infections and mortality posed by formula feeding. In contexts where these risks are not present, such as the UK, guidance recommends that mothers living with HIV stick to formula feeding.

But should the UK guidance change in the light of our increasing understanding of the impact on HIV treatment and undetectable viral load on the risk of transmission? Does the statement “undetectable = untransmittable” (U=U) apply to breastfeeding as well as to sexual transmission?

There are very few data from the UK. Every year, around 1200 babies are born to women living with HIV. Since 2012, just 40 mothers have reported that they have breastfed. All were undetectable and no transmissions have occurred.

Most studies have been conducted in African countries or in India. A recent meta-analysis pooled data from studies on women who were breastfeeding while taking HIV treatment. It found a post-natal transmission rate of 1.1% after six months. Not included in that review, data from 1220 mother-infant pairs in the PROMISE trial showed a post-natal transmission rate of 0.3% after six months and 0.6% after twelve months. This suggests that the transmission risk increases with a longer duration of breastfeeding, although mixed feeding after six months may also have contributed.

Moreover those studies did not correlate mothers’ viral loads with transmissions – mothers whose HIV treatment was not fully effective probably contributed to the transmissions that were seen in those studies. A Tanzanian study reported at the recent European AIDS Conference (EACS) is therefore of interest. Among 177 infants who were exclusively breastfed by mothers living with HIV who began HIV treatment before delivery, there were two transmissions. One was from a mother with a high viral load and the other from a mother who had stopped taking HIV treatment.

In contrast, there were no transmissions from mothers with undetectable viral loads. This suggests that there is a very low risk of breastfeeding transmission when viral load is suppressed, but these are not enough data to say that U=U, Lyall said.

Lyall recommended taking a harm reduction approach with mothers who express a wish to breastfeed. People will make healthier choices if they have access to adequate support, empowerment, and education, she said. Women should be advised that formula feeding has a zero risk of HIV transmission and is the safest thing to do. Breast feeding is an option, but women must understand that they are taking a risk, even if it is a very small risk.

Advice should take account of the risk factors for HIV transmission during breastfeeding. Women who wish to breastfeed should be highly adherent to HIV treatment, have a viral load below 50 copies/ml (ideally throughout the pregnancy), should minimise the duration of breastfeeding, should engage with their multidisciplinary team and should be willing to be followed up monthly.

The Children’s HIV Association (CHIVA) is collaborating with patient advocates to produce patient information which simplifies the complex information on this topic, takes into account women’s preferences and attempts to guide them to the safest approach. It will include three key safety points that women should remember while they breastfeed:

  • No virus: Only breastfeed if your HIV is undetectable.
  • Happy tums: Only breastfeed if both you and your baby are free from tummy problems.
  • Healthy breasts for mums: Only breastfeed if your breasts and nipples are healthy with no signs of injury or infection.

By Roger Pebody

References

Lyall H. Breastfeeding in HIV-positive women. British HIV Association autumn conference, 16-17 November, London. (View the presentation here).

Luoga E et al. HIV transmission from mothers on antiretroviral therapy to their infants during breastfeeding in rural Tanzania. 16th European AIDS Conference, 25-27 October, Milan, abstract PS5/5, 2017.

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Role of the microbiome on HIV infection, prevention and treatment http://www.eatg.org/news/role-of-the-microbiome-on-hiv-infection-prevention-and-treatment/ Wed, 22 Nov 2017 22:45:56 +0000 http://www.eatg.org/?post_type=news&p=6826 The understanding of the human microbiome continues to grow rapidly. Innumerable projects have been launched worldwide to understand the role that the microbiome plays and its impact on human health. However, information on the role of the microbiome on HIV infection, prevention, and treatment is still limited.

Sara Gianella Weibel, MD, on behalf of Infectious Disease Advisor, talks with Nichole Klatt, PhD, associate professor in the department of pharmaceutics at University of Washington in Seattle about the importance of the human microbiome on HIV, including the next steps in research and its relevance in clinical practice.

Infectious Disease Advisor: Dr Klatt, can you tell us about the human microbiome and why is it so important for human health in general?

Nichole Klatt, PhD: The human body harbors 10 to 100 trillion symbiotic microbial cells, with more than twice as many bacterial cells than human cells. Bacteria altogether can constitute several pounds of our body weight. These bacteria are important constituents of the human microbiome and they are an important and very active part of all mucosal tissues and body fluids (oral, gut, genital, skin, airways). In fact, the microbiome is integral in many functions and likely plays a crucial role for the immunologic, hormonal, and metabolic homeostasis of the host.

Infectious Disease Advisor: What factors affect the human microbiome? For example, do we know if there are differences by geographic location, diet, sex or sexual orientation, or other factors?

Dr Klatt: There are certainly geographic differences in microbiome composition and diversity. Recent studies have also demonstrated divergences in the microbiome structure between healthy individuals from different race and ethnicity.1 The microbiome is distinct to each body site, such as lung, oral, gut, penile, and vaginal microbiomes. There are also differences within each anatomic site, such as different parts of the gastrointestinal tract or within the female reproductive tract.2 There are also possibly differences related to sexual practices and lifestyle.

A caveat of microbiome studies, however, is that the use of extremely varied material and methods has led to inconsistent findings, and future larger microbiome studies will need to control for all the behavioral and social factors.

Infectious Disease Advisor: Can we characterize people’s microbiome, and what can this tell us about their health?

Dr Klatt: Different methods can be used to characterize the human microbiome at various mucosal sites, most frequently by sequencing 16s rRNA bacterial genes. In this regard, the American Gut Microbiome Project (which is led by Dr Rob Knight, UCSD) is the world’s largest crowd-funded science project in existence. This initiative is collecting and sequencing stool samples from the entire population and enables participants to learn about their own body’s microbes while also contributing to the greater scientific knowledge. The goal is to learn how the human microbiome is associated with various aspects of our health — from associations with diet to the amount of alcohol consumed to whether or not someone has autism or any other disease. Because all de-identified data are made freely available, researchers from all over the world can access the data to ask questions about the microbiome and its association with a variety of health and lifestyle factors.

Additional advances in our understanding of the microbiome will hopefully provide exciting prospects for exploiting and manipulating the microbiome to improve our health.

Infectious Disease Advisor: Regarding HIV, does the virus itself interact with the human microbiome in either direction?

Dr Klatt: HIV infection is associated with alterations in the gut microbiome, which occur early in the course of infection and are not fully restored with antiretroviral therapy. Mucosal HIV replication and consequent depletion of CD4+ T cells in the gut is associated with epithelial barrier damage (leaky gut) and increased translocation of bacterial products from the gut into systemic blood circulation (microbial translocation). In turn, microbial translocation is associated with systemic immune activation and predicts disease progression and mortality in both untreated and treated HIV-infected individuals.4,5 However, the interactions between HIV, antiretroviral therapy, human sexual behavior, and the gut microbiome are complex and sorting out these interactions will be important to design future interventions. Also, the effect of HIV on the microbiome in other mucosal sites (eg, genital tract, oral) is not as well studied.

Infectious Disease Advisor: You recently published a paper in Science demonstrating that tenofovir efficacy in women depends on the composition of the vaginal microbiome.6 Can you tell us a little more about this study?

Dr Klatt: In our paper, we used stored samples from 688 women enrolled in the CAPRISA 004 clinical trial to investigate whether the composition of the vaginal microbiome modulates the microbicide efficacy of tenofovir gel used as pre-exposure prophylaxis (PrEP) to prevent HIV infection.  In this study, cervicovaginal lavages from women who were assigned to either the tenofovir or the placebo-gel arm were analyzed by protein mass spectrometry and 16s ribosomal RNA sequencing. Our data suggest that women with non-Lactobacillus-dominant vaginal flora have decreased efficacy of tenofovir-based mucosal preventions. On the other hand, bacterial communities rich in Lactobacillus may improve efficacy of topical microbicide gels. Importantly, we found that the mechanism underlying this altered efficacy is likely that dysbiotic bacteria such as Gardnerella vaginalis can directly metabolize tenofovir, likely leading to ineffective levels of tenofovir gel in women with these bacteria. Vaginal microbiota screening could be a useful tool to enhance efficacy of HIV prevention in women.

Infectious Disease Advisor: Do you think that the gut microbiome could have a similar effect on oral antiretroviral therapies?

Dr Klatt: That is a good question and we currently don’t know. Further studies are ongoing to investigate the role of the gut microbiome composition in pharmacokinetics of oral antiretroviral drugs.

It is important to note that one recent study among African women with a high prevalence of bacterial vaginosis found similar efficacy of daily oral PrEP for HIV prevention among women with abnormal vs healthy vaginal microbiota as defined by Nugent score,7 suggesting that the vaginal microbiome is not negatively affecting oral PrEP. However, this needs to be further studied, considering that bacterial vaginosis testing does not accurately measure vaginal microbial dysbiosis, and this should be more carefully evaluated using 16S rRNA sequencing of the microbiome of these women.

Infectious Disease Advisor: Are there any other research questions related to the microbiome and HIV that should be considered?

Dr Klatt: For the future, we need to understand the potential role of other (less well studied) microbiomes, including both non-enteric microbial communities (different body sites) as well as other domains of life beyond bacteria. For example, fungal and viral microbiomes are critical to study. We do know that there is an expansion of the enteric virome during HIV infection, but the exact meaning of this finding is not known.8 For example, certain viruses such as bacteriophage are critical for bacterial regulation, but further studies to understand their exact function and interactions are needed. The fungal microbiome is even less well known. It is clear that fungal species are important in health and there is evidence of increased fungal products in the bloodstream of HIV-infected people, which also correlate with end-organ complications.9,10 However, measurements of these are still underway and critical to better understand the exact interplay of bacteria, viruses, and fungi within the human microbiome at each mucosal site.

The role of non-enteric microbiome is important, too. For example, one recent study found that uncircumcised men who became infected by HIV during the study period had higher levels of penile anaerobes compared with uncircumcised men who remained HIV negative. The authors also reported that having higher levels of penile anaerobes was associated with higher production of certain cytokines that can recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes can also be shared through heterosexual contacts. Modifying the penile microbiome could potentially reduce HIV acquisition in both men and women.11

Even more important than its composition is to understand the exact function of the microbiome. Many questions remain open and we (and other groups) are working hard to understand. For example what do bacteria, fungal, or viral species regulate and how? What bacterial products do bacteria make and how are those relevant for the human host? How do they regulate immunity and epithelial barrier function? How do different bacteria affect drug disposition? Currently, many of these questions do not have clear answers, and many studies are underway and still needed to better understand these questions.

Infectious Disease Advisor: Is there anything we can do (or not do) to maintain a healthy microbiome? Can we correct the microbiome in HIV-infected people using some medications or transplant the “good germs?”

Dr Klatt: The microbiome is very difficult to manipulate. Antibiotics can briefly alter the microbiome, typically with negative consequences for the immune system, and can lead to complications such as Clostridium difficile infection. Once the microbiome is dysbiotic (perturbation of the microbiome, for example in the setting of HIV infection), it is very difficult to revert. Probiotics have demonstrated some encouraging results; however, there is a great variability in different probiotics and how beneficial they are. To date, the best clinical data has come from use of VisbiomeÒ, currently used in an AIDS Clinical Trial Group trial (ClinicalTrials.gov identifier: NCT02706717) to decrease inflammation in HIV-infected individuals. Over-the-counter products such as CulturelleÒ may also have benefits, however, these have not been proven clinically and it is likely that daily dosing is needed to be effective. Alternatives include fecal transplants, but these are quite invasive and have only shown some efficacy in the case of single organism diseases such as C difficile or vancomycin-resistant enterococci infections. The results of fecal transplant in the setting of HIV infection have been variable and are probably not the best approach currently. Early initiation of antiretroviral therapy can partially prevent mucosal damage, although there is evidence that this happens very early during the course of infection.12

We critically need better approaches to enhance the microbiome to improve health in patients with HIV.

References

  1. Gupta VK, Paul S, Dutta, C. Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol. 2017;8:1162.
  2. Chen C, Song X, Wei W, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8:875.
  3. Noguera-Julian M, Rocafort M, Guillén Y, et al. Gut microbiota linked to sexual preference and HIV infection. EBioMedicine. 2016;5:135-146.
  4. Mudd JC, Brenchley JM. Gut mucosal barrier dysfunction, microbial dysbiosis, and their role in HIV-1 disease progression. J Infect Dis. 2016;214 Suppl 2:S58-66.
  5. Zevin AS, McKinnon L, Burgener A, Klatt NR. Microbial translocation and microbiome dysbiosis in HIV-associated immune activation. Curr Opin HIV AIDS. 2016;11:182-190.
  6. Klatt NR, Cheu R, Birse K, et al. Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science. 2017;356:938-945.
  7. Heffron R, McClelland RS, Balkus JE, et al; Partners PrEP Study Team. Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study. Lancet HIV. 2017;4:e449-e456.
  8. Monaco CL, Gootenberg DB, Zhao G, et al. Altered virome and bacterial microbiome in human immunodeficiency virus-associated acquired immunodeficiency syndrome. Cell Host Microbe. 2016;19:311-322.
  9. Hoenigl M, de Oliveira MF, Pérez-Santiago J, et al. (1→3)-β-d-glucan levels correlate with neurocognitive functioning in HIV-infected persons on suppressive antiretroviral therapy: a cohort study. Medicine (Baltimore). 2016;95:e3162.
  10. Hoenigl M, Pérez-Santiago J, Nakazawa M, et al. (1→3)-β-d-glucan: a biomarker for microbial translocation in individuals with acute or early HIV infection? Front Immunol. 2016;7:404.
  11. Liu CM, Prodger JL, Tobian AAR, et al. Penile anaerobic dysbiosis as a risk factor for HIV infection. MBio. 2017;8 pii: 00996-17.
  12. Ericsen AJ, Lauck M, Mohns MS, et al. Microbial translocation and inflammation occur in hyperacute immunodeficiency virus infection and compromise host control of virus replication. PLoS Pathog. 2016;12:e1006048.

 

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Clinical guideline on HBV released by ACP, CDC http://www.eatg.org/news/clinical-guideline-on-hbv-released-by-acp-cdc/ Wed, 22 Nov 2017 22:40:21 +0000 http://www.eatg.org/?post_type=news&p=6829 A new clinical guideline on hepatitis B virus (HBV) urges physicians to vaccinate all unvaccinated adults who are at risk for infection, including pregnant women, and routinely screen at-risk adults.

The American College of Physicians (ACP) and the Centers for Disease Control and Prevention (CDC) published the clinical guideline online on November 20 in Annals of Internal Medicine. The authors also direct clinicians to refer all HBV-infected individuals for appropriate care and counseling.

“Although these topics have been addressed previously in clinical guidelines from the CDC, the U.S. Preventive Services Task Force (USPSTF), the American Association for the Study of Liver Diseases (AASLD), and the Advisory Committee on Immunization Practices, their recommendations vary and implementation has been suboptimal,” Winston E. Abara, MD, PhD, from the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, and colleagues report. “Most persons who are at risk for, are susceptible to, or have HBV infection are not screened, vaccinated, or linked to care,” they write. “Recent studies have suggested additional at-risk groups that should receive HBV screening, treatment, or vaccination that were not in previously published clinical guidelines.”

“The majority of people who are at risk for hepatitis B are not being appropriately screened or if they do have the disease, they are not being referred and linked to care. This is a cost-effective measure and the uptake is way too low,” Jack Ende, MD, president of the ACP, said in a video statement accompanying the report. “Chronic hepatitis B can lead to cirrhosis, liver failure, or primary liver cancer. About 25% of infected patients will die premature[ly] from one of these complications. The HBV vaccination is the most effective way to prevent this illness and therefore its complications,” he said.

The authors reviewed the literature on evidence for HBV vaccination, screening, and linkage to care and integrated new evidence with consensus across guidelines, using a high-value care framework developed by the ACP.

With respect to vaccination, the evidence supports universal vaccination for adults seeking protection from HBV infection and those deemed to be at increased risk for infection as a result of the following:

  • Sexual exposure;
  • Percutaneous or mucosal exposure to blood;
  • Chronic liver disease;
  • End-stage renal disease;
  • HIV infection;
  • Infection risk behaviors during pregnancy; or
  • International travel to regions with high or intermediate levels of endemic HBV infection.

Some of these individuals — particularly those who are immunocompromised or who have end-stage renal disease — may warrant higher vaccine dosages than dosages achieved through the typical three- or four-dose HBV vaccine series to ensure optimal protection, the authors write. Further, they note, “[t]hese persons should receive postvaccination testing, and those with suboptimal response (antibody to HBsAg [hepatitis B surface antigen] level < 10 mIU/mL) should be revaccinated.”

Adverse effects from HPV vaccine are rare and mild, the authors stress. “[T]he most common are soreness at the injection site (3% to 29%) and mild fever (1% to 6%),” they write, noting that postvaccination anaphylaxis is rare, occurring once per 1.1 million doses.

Screening for HBV, via seromarkers for hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen should be conducted in high-risk populations, including

  • Individuals born in countries with 2% or higher HBV prevalence;
  • Men who have sex with men;
  • Intravenous drug users;
  • HIV-positive individuals;
  • Individuals with household and sexual contacts to HBV-infected persons;
  • Individuals requiring immunosuppressive therapy;
  • Individuals with end-stage renal disease;
  • Blood and tissue donors;
  • Individuals infected with hepatitis C virus;
  • Persons with elevated alanine aminotransferase levels (≥19 IU/L for women and ≥30 IU/L for men);
  • Incarcerated individuals;
  • Pregnant women; and
  • Infants born to HBV-infected mothers.

Although current guidelines from the CDC, the USPSTF, and the AASLD recommend screening for persons born in regions with intermediate-to-high prevalence of HBV infection or with other known HBV-related risks, as well as prevaccination testing for healthcare personnel at increased risk for HBV infection and those who perform exposure-prone procedures, “screening in these groups is suboptimal,” the authors write.

The advice also extends to linking HBV-infected individuals to care and counseling as necessary. “Although not all patients with chronic HBV infection require treatment, they all should be routinely evaluated for hepatocellular carcinoma and treatment eligibility through history and physical examination,” the authors state, pointing to evidence indicating that such linkages can significantly reduce HBV-associated morbidity and mortality.

“However, most persons with chronic HBV infection are not linked to care because they are unaware of their infection or are not referred despite their diagnosis,” the authors report. This means that many of the 20% and 40% of individuals with chronic HBV infection who require treatment are not getting it, nor are their liver aminotransferase and HBV DNA levels being monitored, which is recommended for all HBV-infected individuals, they add.

In addition, “[o]nly 10% to 15% of eligible persons receive antiviral therapy, demonstrating that many who could benefit from therapy do not receive it,” the authors explain. “Linkage to care ensures that patients with chronic HBV infection receive treatment when they become eligible (elevated HBV DNA and liver aminotransferase levels), hepatocellular carcinoma surveillance, behavioral risk reduction counseling, and vaccination of susceptible sexual and household contacts,” they state.

For these reasons, all patients identified as HBsAg-positive should be referred for post-test counseling and HBV-directed care.

Multiple patient-, clinician- and system-level barriers prevent optimal uptake of HBV vaccination recommendations, the authors note. Examples include lack of knowledge or information about HBV infection and the benefits of the vaccine in the general public, as well as limited health literacy in certain populations. At the clinician level, lack of awareness of clinical care guidelines or population-specific risks for HBV infection, inadequate screening, and vaccine storage challenges are cited as obstacles. System-level barriers include inadequate funding and challenges associated with specialty referrals, the authors write.

Various strategies for overcoming these barriers are offered, including targeted patient and clinician education, universal screening and vaccination protocols, and culturally sensitive outreach and support.

“The burden and costs associated with chronic HBV infection in the United States are high. Vaccination of susceptible adults is important to prevent infection and reduce ongoing transmission,” the authors state.

However, the existing, risk-based vaccination strategy may be insufficient for increasing HBV vaccine coverage. “Because the administration schedule typically includes 3 vaccine doses over 6 months, the vaccine series needs to be started and completed before exposure to the risk factor to protect persons at greatest risk,” the authors explain. “Furthermore, the multitude of factors constituting an indication for adult hepatitis B vaccination can create implementation challenges for vaccine providers.” For this reason, “[a]n adult vaccination strategy that is not based on risk may be the next step toward achieving elimination.”

One author  reports receiving research grants from Gilead Sciences for hepatitis C treatment and seeing patients who receive free hepatitis C medications supplied by Gilead Sciences in the course of his patient care duties. One author is the treasurer of the ACP. One author reports personal fees from Takeda Pharmaceuticals outside the submitted work and is a member of the ACP Clinical Guidelines Committee and the American College of Rheumatology Quality of Care Committee. The remaining authors have disclosed no relevant financial relationships.

Ann Intern Med. Published online November 20, 2017. Full text

By Diana Phillips

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New findings to help HIV scientists establish ‘template’ for potent antibodies http://www.eatg.org/news/new-findings-to-help-hiv-scientists-establish-template-for-potent-antibodies/ Wed, 22 Nov 2017 22:35:18 +0000 http://www.eatg.org/?post_type=news&p=6822 Natural-infection studies in Africa and India continue to inform HIV vaccine design

New data published today in Immunity further illuminate how some human beings generate powerful, HIV-blocking antibodies. Led by scientists at the International AIDS Vaccine Initiative (IAVI) and The Scripps Research Institute (TSRI), the results offer important insight into a potential AIDS vaccine design.

“Uncovering the process by which neutralizing antibodies develop is critical to HIV vaccine design,” said Elise Landais, Senior Research Scientist with IAVI and lead author of the study. “A small fraction of people living with HIV can naturally produce exceptionally powerful and broad antibodies that could prevent HIV from infecting their immune cells, but not until several years post-infection – long after that protection can help them. But it is of enormous interest to vaccine researchers.”

From samples out of IAVI’s landmark Protocol C epidemiological study, Landais and team selected an African individual infected with HIV subtype-A. Known as PC64, this volunteer developed HIV broadly neutralizing antibodies (bnAbs) targeting the vulnerable V2-apex site on HIV’s surface. This particular type of bnAb is among the most potent, or effective neutralizers of HIV. Their breadth allows them to block the majority of HIV strains.

Applying an advanced technique called next-generation sequencing, the researchers were able to watch these bnAbs develop in reverse. They first took a series of “snapshots” depicting the interplay of PC64’s immune response with the volunteer’s infecting virus over time. Then, using these images, they retraced bnAb development back to the initiation stage, observing that certain viral changes promoted antibody breadth. Follow-up experiments revealed evolutionary similarities between the virus in PC64 and another infecting a CAPRISA study volunteer who developed the same type of bnAbs. The authors also highlighted the impact of additional viral structural attributes.

“These new findings are consistent and complementary with previous work by IAVI and partners and together could offer a possible template for vaccine design,” said Landais. “We’re one step closer to a vaccine that would protect healthy people from HIV infection, but further research is needed to achieve an optimal design.”

Landais et. al. support a sequential immunization strategy, one of several that scientists are collaboratively investigating at the IAVI Neutralizing Antibody Center (NAC) at TSRI. Using data from IAVI’s partner network of clinical research centers in Africa and India, NAC scientists aim to translate laboratory findings into a workable vaccine and other long-acting HIV prevention.

“Development of new and more effective prevention is paramount to ending the HIV/AIDS epidemic,” said IAVI CEO Mark Feinberg. “Of all the tools needed to curb new HIV infections, a vaccine is arguably the most cost-effective and transformative. We’re unlikely to end AIDS without one.”

Landais, Elise et al.: “HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage

DOI: 10.1016/j.immuni.2017.11.002

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Screen all HIV-positive MSM for pre-cancerous anal cell changes, say Dutch investigators http://www.eatg.org/news/screen-all-hiv-positive-msm-for-pre-cancerous-anal-cell-changes-say-dutch-investigators/ Wed, 22 Nov 2017 22:23:57 +0000 http://www.eatg.org/?post_type=news&p=6819

Younger age and shorter duration of viral suppression are risk factors for the development of high-grade pre-cancerous anal lesions in HIV-positive men who have sex with men (MSM), investigators from the Netherlands report in AIDS.

They designed the study to identify demographic and HIV-related risk factors associated with the development of pre-cancerous anal lesions to target men who would benefit from high-resolution anoscopy (HRA). However, the prevalence of such lesions was so high that they recommend that all MSM living with HIV should undergo HRA.

“Of five demographic and seven HIV-related potential risk factors, only increasing age and living with suppressed viral load were significantly protective against HSIL [high-grade squamous intraepithelial lesions] vs. no SIL [squamous intraepithelial lesions],” write the authors. “Sensitivity analyses, including duration of cART [combination antiretroviral therapy] use instead of viral suppression, showed similar results.”

HIV-positive MSM have an increased risk of developing anal cancer. Many treatment centres have established clinics to detect pre-cancerous lesions. An HRA-guided biopsy is considered the gold standard for the diagnosis of these lesions. However, HRA is uncomfortable and costly. It would, therefore, be beneficial to identify the risk factors for pre-cancerous anal lesions so that HRA screening can be appropriately targeted.

Investigators at three clinics in Amsterdam, therefore, designed a study involving 1678 HIV-positive MSM who underwent HRA between 2008 and 2015 (HRA screening was offered to all HIV-positive MSM attedning these clinics). The researchers conducted a series of analyses to see if specific demographic and HIV-related factors were associated with an increased risk of lesions, including HSIL.

The men had a mean age of 49 years and 96% were taking HIV therapy. The median duration of antiretroviral use was a little under eight years and 89% had an undetectable viral load. Median current CD4 cell count was 620 cells/mm3 and median nadir CD4 cell count was 220 cells/mm3. Approximately a fifth of participants had been previously diagnosed with an AIDS-defining illness.

After screening, 24% of men were diagnosed with low-grade pre-cancerous lesions and 30% with high-grade lesions.

Compared to men with no lesions, individuals with low-grade pre-cancerous cell changes were younger (p < 0.001), had higher numbers of recent sex partners (p = 0.016), had a lower number of years on HIV therapy (p < 0.001) and had fewer years of viral suppression (p < 0.001).

Comparison of men with HSIL versus those with no pre-cancerous cell changes identified two factors that were protective against the presence of high-grade pre-cancerous lesions: increasing age (aOR = 0.82; 95% CI, 0.70-0.94, p = 0.006) and increased number of years living with viral suppression (p = 0.009).

These factors remained unchanged in sensitivity analyses.

“Young HIV-positive MSM without viral suppression are statistically at highest risk of HSIL,” conclude the authors. “But given the high prevalence of HSIL among all virally suppressed men, we advise that all HIV-positive MSM should be screened for the presence of anal HSIL.”

By Michael Carter

Reference

Siegenbeek van Heukelom, ML et al. Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible? AIDS 31: 2295-2301, 2017.

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HIV incidence is falling in English gay men, say Public Health England http://www.eatg.org/news/hiv-incidence-is-falling-in-english-gay-men-say-public-health-england/ Wed, 22 Nov 2017 22:19:46 +0000 http://www.eatg.org/?post_type=news&p=6818

While several recent reports have shown that new HIV diagnoses have been falling in UK gay men, what really matters is the actual number of new HIV infections, regardless of whether people are diagnosed or not. This is HIV incidence and Public Health England (PHE) said today (November 15) that, according to their current estimates, incidence among gay and bisexual men in England has been falling since 2012. In previous years, PHE has always believed that incidence was stable.

As HIV incidence includes new infections that have not yet been diagnosed, it is inherently difficult to estimate. The method PHE uses is based on the CD4 counts of men diagnosed with HIV – for example, a man diagnosed with HIV at a CD4 count of 400 is likely to have acquired HIV about four years ago. So new diagnosis data collected this year helps refine the estimates of incidence in previous years.

According to the new estimates, infections in gay and bisexual men have been steadily falling for five years: 2800 infections in 2012, 2100 infections in 2014 and 1700 infections in 2016.

The figures appear in PHE’s annual surveillance report, issued today. While most of the key findings have already been reported by aidsmap in the last few months (here, here, here and here), some interesting extra details are provided. And there is a great deal of new data on HIV testing, covered in another article.

How many people have undiagnosed HIV?

The estimated figures for people with undiagnosed HIV have been falling, bringing England close to meeting the United Nations 90-90-90 targets. It is estimated that 88% of people living with HIV have been diagnosed, 96% of those diagnosed are taking treatment and 97% of those treated have an undetectable viral load.

An estimated 10,400 people living with HIV have not been diagnosed.

  • 13% of gay men living with HIV remain undiagnosed (6100 men).
  • 25% of people who inject drugs living with HIV remain undiagnosed (500 people).
  • 14% of heterosexual men living with HIV remain undiagnosed (1100 men of African ethnicity and 1300 men of other ethnicities).
  • 6% of heterosexual women living with HIV remain undiagnosed (600 women of African ethnicity and 700 women of other ethnicities).

Given the limited data used to calculate these figures, it’s worth remembering that these are all estimates. PHE is more uncertain of its figures for heterosexual men and for people who inject drugs than it is for women and for gay men.

The proportion of gay men who are undiagnosed is lower in London (10%) than it is elsewhere in England (16%).

Three-quarters of heterosexual men who are unaware of their HIV infection are over the age of 35. This is much higher than among undiagnosed women and gay men.

Are diagnoses falling as fast amongst all groups of gay men?

Between 2015 and 2016, new diagnoses in gay men decreased by 21%, from 3570 to 2810. But there are some inconsistencies between different parts of the gay population.

  • Clinic location: while there was a 35% drop in new diagnoses at five central London sexual health clinics, the decrease was lesser elsewhere in London (down by 18%) and elsewhere in England (down by 16%). Without reporting detailed figures, PHE says that clinics in Manchester, Brighton and other cities with large gay populations have also seen above-average decreases.
  • Age: younger men are benefiting the most. In London, the steepest decline in HIV diagnoses was seen among men aged 15-24 years (down 57%), followed by 25-34 year olds (down 33%) and 35-49 year olds (down 17%).
  • Ethnicity: in London, there was a 37% decline in diagnoses in white gay men, comparable to that seen in black gay men (34%), but greater than that seen in Asian men (down 23%) and in men of other or mixed ethnicity (down 26%).
  • Country of birth: in London, the greatest drops were in men born in the UK or in other parts of Europe, with smaller decreases in men born in Latin America, the Caribbean, Asia and Africa.

Where diagnoses are falling, this appears to be due to combination prevention – including condom use, expanded HIV testing, prompt HIV treatment and pre-exposure prophylaxis (PrEP). However, as well as the inequalities within the gay population, combination prevention has not been provided in the same way to heterosexual communities.

“The recent encouraging changes are dependent upon sustained prevention efforts,” comment Public Health England. “The inconsistencies between groups and geographies demonstrate that combination prevention needs to be replicated for all those at risk of acquiring of HIV, whoever they are and wherever they live.”

The health policy organisation The King’s Fund commented that the reduction in new HIV diagnoses is no reason to diminish the HIV response. “This data must be seen as an indicator of the reductions that are possible, rather than meaning that the job is done or that a downwards trajectory in new diagnoses will continue in the future,” they said.

By Roger Pebody

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Who is taking an HIV test in England and where? http://www.eatg.org/news/who-is-taking-an-hiv-test-in-england-and-where/ Wed, 22 Nov 2017 22:15:35 +0000 http://www.eatg.org/?post_type=news&p=6817 No sign that recommendations on frequent HIV testing are being followed by gay men at higher risk of HIV infection

The range of settings in which people test for HIV has expanded significantly in recent years in England, according to a new Public Health England report on HIV testing services. It includes new estimates of the numbers of people who test and re-test for HIV, suggesting that relatively few people at elevated risk of HIV take a test as often as recommended.

While most new HIV diagnoses continue to be made in sexual health clinics, significant numbers are made in a wide range of other settings:

  • Sexual health services (75.4% of male diagnoses and 65.9% of female diagnoses)
  • Hospital wards / in-patient services (6.6% male, 8.8% female)
  • General practices (5.9% male, 7.3% female)
  • Hospital out-patient services (4.1% male, 6.0% female)
  • Antenatal clinics (5.4% female)
  • Community settings (2.5% male, 1.9% female)
  • Other (5.5% male, 4.7% female).

How many people need to be tested to diagnose one person with HIV?

The report compares the effectiveness of different testing services in reaching people with previously undiagnosed HIV. This is another way of looking at the positivity rate of each type of service.

By this measure, self-sampling is one of the most effective services (139 people tested for one reactive result), compared to hospitals and other secondary care services (175 people tested for one diagnosis), community settings (181 people), GPs in high-prevalence areas (217 people) and GPs in extremely high-prevalence areas (228 people).

Overall, sexual health services have a lower positivity rate (442 people tested for one diagnosis). But the figures are much higher in priority populations testing in sexual health services, including gay men (80 men tested for one diagnosis), gay men who’ve recently had a sexually transmitted infection (36 men), people born in high-prevalence countries (127 people) and people of black African ethnicity (145 people). Among people testing in sexual health clinics because they had been told that they had a sexual partner with HIV (partner notification), just 26 needed to be tested for one diagnosis.

When people not belonging to any of the priority groups test in sexual health services, 1333 people need to be tested for one diagnosis. The number of people in the general population is huge while the proportion who have HIV is small. Nonetheless, 29% of all diagnoses made in sexual health services are in people who are not gay men, black African, or born in a high-prevalence country – and late diagnoses frequently occur in people not belonging to obvious risk groups – showing the importance of maintaining HIV testing provision for the wider population.

While self-testing, self-sampling and community testing projects may have high positivity rates, the relatively small scale of these activities means that their overall impact on HIV diagnoses is low. Just over 22,000 people were tested by self-sampling, just over 20,000 through community testing, and just under 27,000 self-testing kits were obtained during 2016. (In contrast, over a million people tested in sexual health services.)

No sign that testing recommendations are being followed by gay men at higher risk of HIV infection

Gay and bisexual men are advised to test for HIV at least once a year – and every three months if they are at higher risk of acquiring HIV. Moreover, men and women of black African ethnicity are advised to have regular tests if having sex without a condom with new or casual partners.

Public Health England’s data suggest that only a minority of people test so frequently, although it should be noted that due to confidentiality protections, individuals cannot be tracked across different sexual health clinics. The clinics know if the same person tests more than once in their clinic during a year, but do not know about tests done at other sexual health clinics, at GPs or elsewhere.

Only 28% of gay men who tested at sexual health clinics had already tested once at the same clinic in the previous year and only 8% had tested at least twice at the same clinic in the previous year. Nonetheless, the figures are better for men with sexually transmitted infections (43%) and overall, the numbers of gay men re-testing within a year have increased by 57% since 2013.

Moreover, 13% of African men or women re-tested at the same clinic within a year.

The report also includes calculations of testing coverage, using estimates of the total populations of gay and bisexual men and of black African men and women. This includes tests done in sexual health services, community settings or self-sampling. It does not include tests carried out in other hospital services, at GP practices or elsewhere.

Just under 126,000 tests were conducted in the approximately 582,000 gay and bisexual men living in England – in other words, just 22% of men tested in the settings that were surveyed. There is substantial regional variation with more men living in London testing (32%) than elsewhere.

There were around 54,000 tests done in the 960,000 African men and women living in England – only 6% of African men and women. The proportion tested was much higher in the West Midlands (23%) and London (13%) than in many other regions (3% or under in the South West, South East, North East, North West and East Midlands).

Public Health England’s data also show an increase in the number of people attending sexual health services who turn down the offer of an HIV test. This has been seen in women born in high prevalence countries (refusals up 56% since 2012), black African women (up 52% since 2012) and people who are not gay men, black African, or born in a high-prevalence country (up 27%).

By Roger Pebody

Reference

Public Health England. HIV Testing in England: 2017 report.

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Up to a quarter of HIV-negative gay men attending three English clinics used PrEP in the last year http://www.eatg.org/news/up-to-a-quarter-of-hiv-negative-gay-men-attending-three-english-clinics-used-prep-in-the-last-year/ Wed, 22 Nov 2017 21:46:05 +0000 http://www.eatg.org/?post_type=news&p=6812 A second survey from one clinic finds 15% were taking PrEP

A prospective cohort study of gay men attending three clinics in southern England – 56 Dean Street and Mortimer Market Centre in London and the Brighton & Hove SHAC (Sexual Health & Contraception) service – have found that 23% of HIV-negative service users who responded to a follow-up questionnaire had used PrEP (pre-exposure prophylaxis) in the last year.

These interim results from the AURAH2 study were presented recently at the 16th European AIDS Conference (EACS 2017) in Milan.

There was tentative evidence that some men may have started switching from PEP (post-exposure prophylaxis) as their favoured method of managing possible HIV exposure.

However, this figure is likely to be higher than the actual proportion of clinic users taking PrEP, as there was a high drop-out rate in the survey and a lot of people who completed baseline questionnaires did not return to fill one out a year later.

A second survey just from Dean Street, conducted last April, found that 15% of its eligible gay male service users who had come in for an STI checkup were taking PrEP.

The AURAH2 Study

The AURAH2 (Attitudes to and Understanding of Risk and Acquisition of HIV over time) Study is a prospective cohort study of gay men attending the three clinics.

AURAH2 recruited its members between 2013 and 2016. HIV-negative men who have sex with men over 18 were included. They were given a baseline paper questionnaire to fill in at the start of the study and were then asked to fill in an online follow-up questionnaire every four months.

The questionnaires asked about HIV testing, health and lifestyle factors (including recreational drug use and chemsex), recent sexual behaviour and, once a year, PEP and PrEP use.

Although 1167 men completed the baseline questionnaire, only 53% of them (620) subsequently filled in a follow-up online questionnaire and 467 men (40%) provided at least one annual questionnaire about PEP and PrEP use.

In the baseline questionnaires, the average age of participants was 31, 84% were white, 40% were in a relationship, 77% said they were without significant money worries and 83% were in employment. Twenty-one per cent were current smokers, 21% drank the amount of alcohol classed as “higher risk” by the World Health Organization, and 61% had used recreational drugs in the last three months.

The characteristics of the 476 men answering the PEP/PrEP questionnaire were similar, with the exception that slightly fewer of them (16 vs 23%) had significant money worries.

Because recruitment into the survey took three years, there were changes between the answers given in baseline questionnaires collected in the latter half of 2013, when recruitment started, and ones collected in the first half of 2016, after which it finished.

The proportion aware of PEP was already high and stayed so at about 95% but the proportion who had ever taken it more than doubled from 21% to 49%.

Awareness of PrEP more than doubled, from 43% to 92%. The proportion who had actually taken it tripled, from 4% in 2013 to 11% in 2016.

In the one-year follow-up questionnaire, the proportion who had taken PEP in the year since entering the study did not change overall between the latter half of 2015 (when the first year-one questionnaires were analysed) and the middle of 2017, date of the most recent ones. But the proportion who had taken PrEP during the year doubled, from 12% to 23%. This 23% represented 110 men.

There was an early hint that some might be switching from PEP to PrEP. Till the first quarter of 2017, PEP use looked as if it was on an upward trajectory, with 20% who answered the questionnaire during that quarter recording PEP use in the last year. In the second and third quarters of 2017, it fell to 10%, but it is too early to say if this is a trend or a random finding.

PrEP takers were asked where they had acquired PrEP: 50% said they had bought it on the internet, 39% got it from a doctor, and 11% acquired it both online and from their doctor. As all three clinics participated in the PROUD study, many or most of the 55 men who reported getting it from their doctor may have been in that study.

AURAH2 is still ongoing: its last annual questionnaires will be collected in March 2018, and it will be interesting to see if PrEP use increases due to these clinics being part of the IMPACT study. However, it is clear that still only a minority of gay men who might benefit from PrEP are taking it.

Three-day Dean Street survey finds roughly similar proportion on PrEP

A letter published in Sexually Transmitted Infections journal recently provided more context. It was a survey of patients who attended the Dean Street Express clinic in London over just three days in April 2017.

The clinic provided 507 STI tests in those three days – 169 a day. Seventy service users (14%) had HIV. Of the other 437, 17% (87 men) said they always used condoms and four had had no sexual partners in the last three months.

Fifty-two (15%) of the remaining 352 were taking PrEP and 11 (3%) were currently taking a course of PEP. This left 64% of all testers eligible for PrEP, but either not taking it or not replying to the question – 45% said they definitely had not taken it. This 15% is at least roughly in the same ballpark as the proportion found in AURAH2.

Men who were taking PrEP were more likely to have had condomless anal sex in the last three days (27 vs 12%); were more likely to have had condomless anal sex as the receptive partner in the last three months (90 vs 76%) and had had an average of eight vs four partners, as the receptive partner, during that time.

By Gus Cairns

References

Cambiano V et al. Changes over Time in PrEP Use among Gay/Bisexual Men in England: Data from the AURAH2 Study. 16th European AIDS Conference, 25-27 October, Milan, abstract PS12/5, 2017.

Whitlock GG et al. How many MSM are taking PrEP: a service evaluation. Sexually Transmitted Infections Volume 93, Issue 7. 2017.

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Gay men’s stories of monogamy and non-monogamy: change, flexibility and tensions http://www.eatg.org/news/gay-mens-stories-of-monogamy-and-non-monogamy-change-flexibility-and-tensions/ Wed, 22 Nov 2017 20:20:55 +0000 http://www.eatg.org/?post_type=news&p=6814

Although some gay men idealise monogamy, particularly in the early stages of a relationship, couples often become non-monogamous over time, Australian researchers report in an article published online ahead of print in Culture, Health and Sexuality.

Men often saw non-monogamy as realistic in gay relationships, due to social and cultural norms in gay communities. But shifting the ground rules of relationships could be challenging for some couples, especially when the partners had different values about monogamy and non-monogamy.

For this qualitative study, Steven Philpot and colleagues conducted in-depth interviews with 61 Australian gay men. The interviews explored issues of intimacy, relationships and monogamy with men who were either single or in a couple at the time of the interview.

HIV is frequently transmitted within committed relationships, so a better understanding of relationship dynamics is important for HIV prevention.

Expectations

Many men, particularly younger men, implicitly expected monogamy to be the basis for long-term relationships. They felt it created stability, security, intimacy and trust. It was seen representing a more moral way of life than non-monogamy and promiscuity.

“We never discussed being completely exclusive: it was just a given that we would only see each other.” (Single, 21 years).

“Even though I’m gay I still believe in the whole stable family thing. So, I do want a husband and kids.” (Coupled, 22 years).

Nonetheless, men did not necessarily think that monogamy would last. It might be thought of as most important at the beginning of a relationship:

“I think it’s important to have monogamy for at least the first three years of your relationship because it creates emotional connections and a spiritual connection. And because in the first three years of your relationship, that’s all new and you don’t want to rip that out and have that strain put on the relationship.” (Single, 29 years).

Many men expected relationships to transition to non-monogamy over time. While some men explained this by talking about the ready availability of sex on the gay scene, others gave biological explanations:

“When you’ve got two hormonally driven men sometimes they just need an outlet if they don’t want to self-destruct.” (Single, 24 years).

The same man also said that social contact with other gay couples had led him to expect a non-monogamous relationship, even if he struggled with this expectation.

“Most people in relationships I know that have lasted are open so even though I don’t like it, I am aware that if I want a lasting relationship, there’s a good chance that’s the key to success.”

In contrast, other men aspired to non-monogamy. They might idealise older couples whose relationships were secure, successful and open:

“They’re deeply in love and they’ve got a home together. And they’re in a completely open relationship… That’s something I would like as well. It’d be nice to get to that point in time where insecurities have gone and you don’t worry about who’s sleeping with who, so long as you love the person you’re going home to… If [partner] and I do stay together long-term, that’s where I see our relationship going.” (Coupled, 28 years).

Change

Most often, relationship expectations shifted from monogamy to non-monogamy, over a period of time. This man’s expectations changed several years into his relationship:

“I wanted a heterosexual version of relationships, and monogamy was important. And then, I can’t remember thinking too much about that in the first few years, but probably five years into it we started talking about a threesome and that occurred. And that worked well for us.” (Coupled, 49 years).

The most common motivation for moving from monogamy to non-monogamy was sexual dissatisfaction. Some men were more interested in sex than their partner, had sexual interests that their partner could not accommodate, or were less attracted to their partner than before.

Non-monogamy offered a practical solution to the issues they faced in maintaining a regular and satisfying sexual life without the risk of losing their primary relationship.

“The physical side of our relationship was an issue. I had a high libido and my partner didn’t… We tried different things, and one of them was there was tolerance for sexual activity outside of the relationship.” (Coupled, 27 years).

In making changes, a number of men felt that rules could be helpful.

“I would ensure there were rules and a common understanding. And for me, the only way that any open relationship would work was if both parties understood what certain actions meant, both emotionally and ideologically. Is it okay to sleep with this person under this condition? Do we need permission from each other before we do this?” (Coupled, 30 years).

Many men in non-monogamous relationships emphasised the importance of emotional commitment. They described non-monogamy in ways which reflected the emotional and romantic centrality of their primary relationship, while contesting the idea that they should only have sex with that man.

They also challenged the idea that being in a non-monogamous relationship meant their life was a frenzy of casual sex.

“As it turned out, I wasn’t constantly thinking about it. It was like the freedom to have sex with a third party made me less inclined to think about it.” (Coupled, 47 years).

“There’s nothing wrong with us going out and having fun with somebody else, but it’s not like we go searching for it.” (Coupled, 41 years).

A number of men described flexibility in their relationships. They saw their desires and needs as changeable and emphasised trust, communication and a willingness to compromise. They did not describe a linear movement from monogamy to non-monogamy:

“It’s a fluid thing. It really opens, and closes, and maybe opens again.” (Coupled, 26 years).

And other couples shifted from non-monogamy towards monogamy:

“In the early days we were more open and adventurous with other guys but that drifted and we said, ‘What’s the point? We’re happy with each other’, and that just fizzled out.” (Coupled, 62 years).

Negotiating change

The sociologist Anthony Giddens has described gay men as “emotional pioneers” in pursuing non-monogamous relationships. He portrayed these relationships as egalitarian, with few differences of power, and allowing both partners to maintain personal autonomy.

However interviewees’ accounts of making changes to their relationships sometimes revealed power imbalances and tensions. A number of men who preferred monogamy acquiesced or reluctantly accepted their partner’s desire for an open relationship.

“I don’t think I was ever happy with it but I was like, ‘I’ll give it a go.’ And at the time I didn’t think it’d be quite as non-monogamous as it was… We were equally free to do whatever we wanted outside the relationship but I took little advantage of that whereas my partner took lots of advantage.” (Coupled, 43 years).

“He said he didn’t care if his partner goes off and sleeps with some else. But he would never do it. I don’t like that because that means that I would have an upper hand in the relationship. I would have the balance of power. I like a relationship to be equal and on equal terms. If I can do it, you can do it too, and you shouldn’t feel like you shouldn’t be able to.” (Single, 22 years).

Men who acquiesced generally did so for fear of losing their partner, thus making the relationship inherently unequal. They often remained dissatisfied, for example feeling jealous, envious or distrustful. In a number of cases, the relationship broke down.

Social norms within gay communities could also have an impact on partners’ negotiation. Some partners who preferred non-monogamy were able to suggest that it was a more progressive option or one that was informed by a better understanding of how gay relationships can work. As a result, men who preferred monogamy could be positioned as more conservative or less experienced, therefore holding less sway in the discussion.

Some men, who were generally older, described guiding a less experienced partner towards acceptance of non-monogamy.

“He took it differently than I do because he was so young and I was older… There’s been a few instances where I’ve helped him push his boundaries because I’ve had more experiences in things like sex clubs. And some of them he was terrified. We went earlier this year and I said, ‘I’d love you just to experience a sex club. You don’t have to do anything.’ And we went to one and he was pleasantly surprised.” (Coupled, 41 years).

The less experienced partners often appreciated such guidance.

“One of the revelations of living with [partner] is that from the beginning he was completely supportive of an open relationship. In fact, he introduced me to [the] concept. He said, ‘It’s impractical to expect you to be faithful to me and vice versa.’ I guess I admire his lack of jealousy.”

Steven Philpot says that the findings shed light on how gay men deal with changing expectations of fidelity within their relationships, and the tensions and opportunities that change produces for couples.

By Roger Pebody

Reference

Philpot SP et al. Negotiating gay men’s relationships: how are monogamy and non-monogamy experienced and practised over time? Culture, Health & Sexuality, online ahead of print, 2017. (Abstract).

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Review identifies aspects of healthcare most valued by people with HIV http://www.eatg.org/news/review-identifies-aspects-of-healthcare-most-valued-by-people-with-hiv/ Wed, 22 Nov 2017 20:12:44 +0000 http://www.eatg.org/?post_type=news&p=6821

–Systematic review identifies the healthcare factors most valued by people living with HIV.
–Relationship with healthcare providers cited in 83% of studies reviewed, and treatment information and support in 63%.
–People with HIV place value on provider’s expertise, confidentiality and coordination, and on ease of access and active participation as a client.

It is important to understand what people with HIV value most in their healthcare experience to deliver services that best respond to their needs and keep them engaged in care over the long term. To examine this, researchers in the United Kingdom conducted a systematic review on the aspects of healthcare valued by people with HIV. They identified seven areas of importance for patients: relationship with their healthcare provider; expertise of their healthcare provider; access to care; receipt of information and support; coordination between the services they receive; confidentiality; and participation in their care.

Review details

A systematic review is a critical summary of the available evidence on a specific topic. It uses a rigorous process to identify all the studies related to a specific research question. Relevant studies are then assessed for quality and their results summarized to identify and present key findings and limitations.

The systematic review included 23 studies published between 1996 and 2015.The studies took place in high-income locations including Canada, the United States, the United Kingdom, the Netherlands and Australia. Almost half the studies took place in the United States. Data gathering methods included interviews and/or focus groups, questionnaires, rating of different aspects of care and a card-sorting exercise.

Results

The review grouped the results of the 23 studies into seven themes.

1. Relationship with their healthcare provider

In 83% of studies (19/23), participants valued the relationship they had with their healthcare provider. This included valuing interpersonal factors, like comfort sharing personal issues with their healthcare provider, and personal characteristics of their provider, such as compassion, that helped respondents feel respected and supported.

2. Expertise of their healthcare provider

The expertise of healthcare providers was a valued aspect of care in 39% of studies (9/23). People with HIV valued their provider’s current, specialist knowledge of HIV. Concern was raised in some studies by respondents who perceived general primary care physicians as having insufficient knowledge or experience of HIV to deliver care to people with HIV.

3. Access to care

Easy access to healthcare was valued by people with HIV in 39% of studies (9/23). This included timely access to care, convenient clinic hours, timely response to phone calls, transparency of services, such as the ability to access personal health records, and reliability of services.

4. Receipt of information and support

People with HIV valued the receipt of accessible information to help them understand their treatment and care in 61% of studies (14/23). Clear and easy to understand information was important, specifically regarding HIV treatment, including side effects and the benefits and drawbacks of treatment. They also valued information and support with other areas of their life such as finances or immigration, as well as support from peers.

5. Coordination between services received

People with HIV reported that they valued good coordination and communication between the healthcare professionals involved in their care in 25% of studies (6/23). They also valued being linked to other services in their community such as housing or mental health services.

6. Confidentiality

People with HIV were concerned about confidentiality of their HIV status in 35% of studies (8/23). This included concerns about unintended disclosure if they were seen in a location providing HIV-related services, or the need for disclosure and concerns about stigma and discrimination when accessing services beyond their HIV-specific care.

7. Participation in their careActive participation in their heathcare was valued by people with HIV in 26% of studies (6/23). Some examples of healthcare participation included working in partnership with their healthcare provider, making the final decision about their care and maintaining personal records of their care.

Comparing aspects of care

While the variety of methods used and aspects of care examined did not make it possible to compare the importance of themes across studies, the relationship with a healthcare provider and receipt of information and support to help people with HIV manage their care were the themes that occurred most often. None of the studies examined the relative importance of all seven themes identified by the review. However, six studies did assess the relative importance of selected aspects of care, with the relationship with and expertise of healthcare providers often given high importance.

Implications for care

This systematic review provides insight into the aspects of care valued by people with HIV. The seven themes identified highlight patient preferences that can inform the delivery of HIV care, with the ultimate goal of improving engagement in care and health outcomes. Looking across themes, some implications for care include:

  • The quality of the relationship with their care provider was the aspect of care valued most frequently across studies. People with HIV also valued the expertise of their care provider. For people receiving care from general primary care physicians who may not have specialist knowledge of HIV, HIV-specific training may be beneficial for providers and contribute to patient confidence in their care.
  • People with HIV valued receiving accessible information to help them understand their treatment and care. They also valued being participants in healthcare decision-making. Providing information that is clear and easy to understand and otherwise supporting people who choose to take an active role in their care may help people feel more engaged in their care. People also valued the support of peers in peer programs.
  • People valued timely access to care and improved coordination of care among members of the healthcare team and through support and linkages with other services in the community. Models of care that facilitate coordination and communication among services may help to address diversifying care needs.
  • Fear of stigma and discrimination is still a concern for people with HIV and services that prioritize the confidentiality of a person’s HIV status can help to address this barrier to care.

Bear in mind

The quality of the studies included in the review varied greatly with just over half of studies (13/23) assessed as being of good quality. Additional research with more rigorous methodology will help confirm the findings in this review. The authors were also unable consider the results by demographic characteristics, such as age or ethnicity. These findings may not be generalizable across all populations, with different populations possibly valuing unique aspects of care.

By Erica Lee

References

Cooper V, Clatworthy J, Youssef E, et al. Which aspects of health care are most valued by people with HIV in high-income countries? A systematic review. BMC Health Services Research. 2016 Nov 30;16(1):677.

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No benefits for protease inhibitor plus raltegravir as second line in HIV http://www.eatg.org/news/no-benefits-for-protease-inhibitor-plus-raltegravir-as-second-line-in-hiv/ Wed, 22 Nov 2017 20:10:38 +0000 http://www.eatg.org/?post_type=news&p=6827 A recent study showed that treatment with a protease inhibitor plus raltegravir offered no benefit over a protease inhibitor plus nucleoside reverse-transcriptase inhibitor (NRTI) regimen in patients with HIV.

James G. Hakim, MD, from the University of Zimbabwe Clinical Research Centre, Harare, and colleagues published the results of their study November 3, 2017, in the Lancet Infectious Diseases.

“Taking into account the higher cost of raltegravir, the absence of clear advantages of protease inhibitor plus raltegravir seen in any trial and the failure to show non-inferiority consistently across all analyses after 144 weeks of treatment in this trial suggest that there is no compelling reason for national programmes to adopt this combination as the standardized second-line therapy in the public health approach to antiretroviral therapy,” the authors write.

For patients with HIV, World Health Organization (WHO) guidelines currently recommend 2 NRTIs and a boosted protease inhibitor for second-line treatment antiretroviral therapy (ART), and suggest a protease inhibitor plus raltegravir as an alternative regimen.

According to Dr. Hakim and colleagues, however, resistance to NRTIs occurs after virological failure of first-line treatment in low-income countries, and this may affect future treatment options.

The researchers therefore conducted the EARNEST trial to investigate alternatives for second-line treatment. They wanted to determine whether the WHO-recommended regimen offers any benefit to patients with HIV over the standard protease inhibitor plus 2 NRTIs regimen.

The trial enrolled 1277 patients with HIV who had extensive resistance at randomization; 95% of patients had at least 1 NRTI mutation, and 59% had no active NRTIs.

Patients were randomly assigned to receive either: a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus 2 or 3 NRTIs (protease inhibitor plus NRTI group); a protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group); or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group).

The researchers followed the patients for 144 weeks.

Despite extensive NRTI resistance, the researchers found that the protease inhibitor plus NRTI group performed better than the other non-NRTI groups, with 86% of 426 patients having viral loads of less than 400 copies per mL by week 144, compared with 81% patients in the protease inhibitor plus raltegravir group, and 78% patients in the protease inhibitor monotherapy group.

“There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification,” the authors add.

The results of this study have important implications for the selection of second-line therapy in the public health approach to ART.

“The good longer-term outcomes with the combination of a protease inhibitor (in this case lopinavir) with 2 NRTIs provides support for this regimen as the WHO-recommended preferred second-line combination,” the authors conclude.

By Nicola Parry

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Hepatitis increases mortality rates in HIV patients http://www.eatg.org/news/hepatitis-increases-mortality-rates-in-hiv-patients/ Wed, 22 Nov 2017 20:05:30 +0000 http://www.eatg.org/?post_type=news&p=6828 Patients with HIV coinfected with hepatitis B (HBV) or hepatitis C (HCV) have a significantly greater risk of all-cause or liver-related mortality than those individuals who are HIV mono-infected, a study in AIDS reports.

Alicia C. Thornton, PhD, of the Research Department of Infection and Population Health at University College London in the UK, and colleagues compared all-cause, liver-related, and AIDS-related mortality rates in mono-infected HIV patients with those rates in co-infected HBV and HCV patients.

A total of 25,486 HIV patients across 11 UK-based clinics were tested for HBV using a hepatitis B surface antigen (HBsAg) test and HCV using an antibody or HCV RNA test. Causes of death were labeled liver-related, AIDS-related, or neither (all-cause). Liver-related death was defined as death due to decompensated liver disease, hepatocellular carcinoma and liver failure, and metastasized liver cancers.

Patients were categorized in AIDS-related deaths if AIDS was stated as a cause of death or if the cause of death included AIDS-defining illnesses (using the list of conditions from the CDC).

Of the patients who were HIV-positive before 2004 (121,814 person-years), 4.2% died during their follow-up time (median follow-up time was 4.6 years per person). Once test results were received, patients were grouped as HIV-monoinfected (89%), HIV/HBV-coinfected (47%), HIV/HCV-coinfected (5.5%), or HIV/HBV/HCV-triple-infected (0.49%).

The researchers found that all categories of hepatitis-coinfection are significantly associated with an increased risk of all-cause mortality, namely patients with triple infection, who have a 2.29 times greater risk of death than HIV-monoinfected patients. Also significant, HIV/HBV patients (ARR, 1.6) and HIV/HCV patients (ARR, 1.42) have a greater risk of death than HIV-monoinfected patients.

Liver-caused deaths were much more significant than all-cause rates in all three infection categories. Compared with HIV-monoinfection, the highest risk of mortality was associated with HIV/HBV/HCV (ARR, 15.19), followed by HIV/HBV (ARR, 10.42), and HIV/HCV (ARR, 6.2).

Hepatitis coinfection was not significantly involved in increasing mortality associated with AIDS, as HBV is not associated with an increase progression of HIV to AIDS. In addition, HIV/HCV-coinfected patients had a significantly lower risk of AIDS-related mortality compared with HIV-monoinfected patients (ARR, 0.4).

The findings emphasize the needs for primary prevention and effective hepatitis treatments for HIV-positive patients.

“Directly acting agents for treatment of HCV infection are now available, which have high rates of cure,” stated the authors. “If patients are able to access these treatments the increased risk of mortality from HCV infection may be mitigated.”

By Rita Aghjayan

Reference

Thornton AC, Jose S, Bhagani S, et al. Hepatitis B, hepatitis C, and mortality among HIV-positive individuals. AIDS. 2017;31(18):2525-2532. doi: 10.1097/QAD.0000000000001646

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Second HIV test helps prevent incorrect HIV diagnosis in infants http://www.eatg.org/news/second-hiv-test-helps-prevent-incorrect-hiv-diagnosis-in-infants/ Wed, 22 Nov 2017 19:58:54 +0000 http://www.eatg.org/?post_type=news&p=6823

Confirmatory HIV testing can substantially reduce the number of infants in South Africa who may be falsely diagnosed as HIV-infected and started on unneeded treatment, according to a new study published this week in PLOS Medicine by Lorna Dunning of the University of Cape Town, South Africa, and colleagues. Confirmatory testing is recommended by the World Health Organization and South African guidelines, but in many settings, uptake is low.

The specificity of nucleic acid amplification tests (NAATs) for early infant HIV diagnosis (EID) is less than 100 percent, meaning some infants are incorrectly diagnosed with HIV. Using an existing computer simulation model of pediatric HIV, the authors of the new study examined the impact of a second NAAT in infants to confirm a first positive result. They assumed a NAAT cost of $25, specificity of 99.6%, and sensitivity of 100%.

Without confirmatory testing, 128 of every 1000 infants initiating antiretroviral therapy (ART) were actually HIV-uninfected, due to false-positive diagnoses; with confirmatory testing, only 1 out of 1000 infants initiating ART was truly uninfected. Because a second round of testing averted costly and unnecessary HIV care and ART in HIV-uninfected infants, the additional testing was projected to be cost-saving over a lifetime, costing $1,790 per infant tested, compared to $1,830 without confirmatory testing. The study went on to show that when confirmatory testing is used, ART should be initiated immediately after a first positive NAAT. Waiting even one month until the return of a second test to initiate ART can markedly reduce both short-term and long-term survival for HIV-infected infants.

“We find that use of a second NAAT for confirmatory testing in EID programmes will substantially reduce the proportion of infants incorrectly diagnosed as HIV-infected and initiated on ART in settings with low infant HIV transmission rates like South Africa” says Ms. Dunning. “While projected cost differences are small, confirmatory testing is likely to be cost-saving under a wide range of scenarios in South Africa,” notes Dr. Andrea Ciaranello of Massachusetts General Hospital and Harvard Medical School, senior author on the study. “Concerns about the cost of the second test itself should not be the reason to avoid this important intervention.”

Journal Reference:

  1. Lorna Dunning, Jordan A. Francke, Divya Mallampati, Rachel L. MacLean, Martina Penazzato, Taige Hou, Landon Myer, Elaine J. Abrams, Rochelle P. Walensky, Valériane Leroy, Kenneth A. Freedberg, Andrea Ciaranello. The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis. PLOS Medicine, 2017; 14 (11): e1002446 DOI: 10.1371/journal.pmed.1002446
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Schistosomiasis increases risk of infection with HIV, especially for women and is also associated with a higher HIV viral load http://www.eatg.org/news/schistosomiasis-increases-risk-of-infection-with-hiv-especially-for-women-and-is-also-associated-with-a-higher-hiv-viral-load/ Wed, 22 Nov 2017 19:52:34 +0000 http://www.eatg.org/?post_type=news&p=6813

Infection with schistosome parasitic worms has an important role in HIV transmission, especially for women, and may accelerate HIV disease progression, according to research published in PLOS Neglected Tropical Diseases. Women with schistosomiasis had a three-fold increased risk in becoming infected with HIV, compared to women who did not carry the worms. Moreover, HIV viral load after infection was higher among schistosome-infected individuals, increasing both their potential infectiousness to sex partners and the risk of HIV disease progression.

“Our study suggests that interactions exist between HIV-1 and schistosomiasis that may play a critical role in HIV-1 transmission and disease progression in African countries,” comment the investigators.

Schistosomiasis is a disease caused by a tropical parasitic worm infection. Over 90% of infections occur in Africa. The worms live in small veins in host’s pelvis and gut and daily lay hundreds of eggs that migrate to the urogenital and gastrointestinal mucosa where they cause inflammation and physical breaches in the mucosa.

A team of investigators postulated that pre-existing schistosome infection would increase a patient’s risk of acquiring HIV, with the risk especially high for women. They also hypothesised that individuals with active schistosome infection at the time of HIV acquisition would have impaired immune systems, resulting in higher HIV viral loads.

To test these hypotheses, the researchers designed a nested case-controlled study involving adults living in rural Tanzania. In 2007, 2010 and 2013 participants were tested for HIV.

The investigators identified 73 individuals who became infected with HIV during follow-up. These people were matched with 265 controls who remained HIV negative. Dried blood spots from the cases and controls were tested for the presence of schistosome infection to see if it increased the risk of acquiring HIV.

The investigators also compared the viral loads of HIV seroconverters according to schistosome-infection status.

In women, 44% of those who acquired HIV had schistosome infection at the time of their seroconversion compared to 30% of the HIV-uninfected controls. After taking into account potential confounders, the investigators showed that women with schistosome infection had an almost three-fold increase in the risk of becoming infected with HIV compared to women who remained HIV negative (OR = 2.8; 95% CI, 1.2-6.6, p = 0.019).

Just under a third (29%) of men who seroconverted for HIV had schistosomiasis at the time they became infected with HIV, compared to a schistosomiasis prevalence of 38% among men who remained HIV negative. As such, the schistosome infection did not increase the risk of HIV acquisition for men.

“We found that schistosomiasis increases the odds of HIV-1 acquisition in women but not men,” comment the researchers. “This strong gender effect may be due to differential effects of schistosome eggs in the genital mucosa of women versus men.”

Among people who did become infected with HIV, median viral load was approximately 25,000 copies/ml among those with schistosomiasis compared to 5000 copies/ml among individuals who did not carry the parasitic infection, a significant difference (p = 0.017). Viral load differences by schistosomiasis-infection status were more pronounced in women.

“We found that schistosomiasis at the time of HIV-1 infection led to a 0.7 log10 increase in viral load at the time of HIV-1 seroconversion,” write the authors. “A sustained 0.7 log10 HIV-1 load increase equates with an approximate doubling of infectivity among HIV-1-schistosome co-infected individuals and would be expected to accelerate time to symptomatic AIDS or death by 2-3 years.”

The authors conclude that schistosomiasis increases HIV incidence among women and raises viral load at the time of seroconversion. They note that praziquantel is a cheap and safe treatment for schistosomiasis and call for studies to determine the effectiveness of mass therapy with this drug to decrease HIV transmission and slow HIV disease progression.

By Michael Carter

Reference

Downs JA et al. Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: a nested case control study. PLOS Negl Trop Dis 11 (9): e0005968. https://doi.org/10.1371/journal.pntd.0005968 (2017).

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UNAIDS announces nearly 21 million people living with HIV now on treatment http://www.eatg.org/news/unaids-announces-nearly-21-million-people-living-with-hiv-now-on-treatment/ Tue, 21 Nov 2017 22:59:04 +0000 http://www.eatg.org/?post_type=news&p=6810

New report from UNAIDS highlights the right to health as the key to ending AIDS

CAPE TOWN/GENEVA, 20 November 2017—Remarkable progress is being made on HIV treatment. Ahead of World AIDS Day, UNAIDS has launched a new report showing that access to treatment has risen significantly. In 2000, just 685 000 people living with HIV had access to antiretroviral therapy. By June 2017, around 20.9 million people had access to the life-saving medicines. Such a dramatic scale-up could not have happened without the courage and determination of people living with HIV demanding and claiming their rights, backed up by steady, strong leadership and financial commitment.

“Many people do not remember that in 2000 there were only 90 people in South Africa on treatment,” said Michel Sidibé, Executive Director of UNAIDS, speaking in Khayelitsha, South Africa. “Today, South Africa has the biggest life-saving treatment programme in the world, with more than 4 million people on treatment. This is the kind of acceleration we need to encourage, sustain and replicate.”

The rise in the number of people on treatment is keeping more people living with HIV alive and well. Scientific research has also shown that a person living with HIV who is adhering to an effective regime of antiretroviral therapy is up to 97% less likely to transmit HIV. As treatment access has been scaled up for pregnant women living with HIV, new HIV infections among children have been rapidly reduced. From 2010 to 2016, new HIV infections among children were reduced by 56% in eastern and southern Africa, the region most affected by HIV, and by 47% globally.

“In 2001, the first person in Khayelitsha started HIV treatment. Today, there are almost 42 000 people on treatment here. The success of Khayelitsha’s treatment programme is a microcosm of the massive success of South Africa’s HIV programme,” said Aaron Motsoaledi, Minister of Health, South Africa.

The challenges now are to ensure that the 17.1 million people in need of treatment, including 1.2 million children, can access the medicines and to put HIV prevention back at the top of public health programming, particularly in the countries in which new HIV infections are rising.

The new report from UNAIDS, Right to health, highlights that the people most marginalized in society and most affected by HIV are still facing major challenges in accessing the health and social services they urgently need. However, the report also gives innovative examples of how marginalized communities are responding.

In India, for example, a collective of sex workers has trained sex workers to work as nursing assistants, providing stigma-free health services to sex workers and the wider community. In Uganda, groups of grandmothers are weaving and selling traditional baskets to allow them to pay for schooling for the grandchildren in their care who lost their parents to AIDS.

In 2016, around 1.8 million people were newly infected with HIV, a 39% decrease from the 3 million who became newly infected at the peak of the epidemic in the late 1990s. In sub-Saharan Africa, new HIV infections have fallen by 48% since 2000.
However, new HIV infections are rising at a rapid pace in countries that have not expanded health and HIV services to the areas and the populations where they are most effective. In eastern Europe and central Asia, for example, new HIV infections have risen by 60% since 2010 and AIDS-related deaths by 27%.

References to the right to health are found in international and regional laws, treaties, United Nations declarations and national laws and constitutions across the globe. The right to health is defined in Article 12 of the International Covenant on Economic, Social and Cultural Rights as the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. This includes the right of everyone, including people living with and affected by HIV, to the prevention and treatment of ill health, to make decisions about one’s own health and to be treated with respect and dignity and without discrimination.

UNAIDS’ Right to health report makes it clear that states have basic human rights obligations to respect, protect and fulfil the right to health.

The report gives voice to the communities most affected by HIV—including people living with HIV, sex workers, people who use drugs, gay men and other men who have sex with men and young people—on what the right to health means to them.
“Almost 20 years ago, the struggle was about access to treatment. Now, my struggle is not only about access but about ensuring that I have the support that I need to live a healthy and positive life. That is my right to health,” said Cindy Mguye, civil society representative.

Wherever the right to health is compromised, HIV spreads. In sub-Saharan Africa, for example, 67% of new HIV infections among young people are among young women and girls aged between 15 and 24 years. Studies have shown that a large number of young women and girls in the region contract HIV from older men, demonstrating multiple concerns about the ability of young women and girls to negotiate safer sex, stay in education and access age-appropriate sexual and reproductive health services.

Studies have also shown the difficulties health services face in reaching men with HIV testing and treatment, as well as broader health services, showing the challenge in encouraging men to exercise their right to health. In 2016, men in sub-Saharan Africa were 18% less likely to be accessing treatment and 8% more likely to die from AIDS-related illnesses than women.

The Right to health gives a clear demonstration of the challenges ahead in efforts to end the AIDS epidemic as a public health threat by 2030, as outlined in the 2016 United Nations Political Declaration on Ending AIDS.

The report underscores that to reduce new HIV infections and AIDS-related deaths and ensure access to essential health services, funding for health needs to increase. It gives examples of how to enhance funding, including increasing the share of health spending as a proportion of national economies, making savings through efficiencies and partnering with the private sector. The funding gap for HIV is estimated at US$ 7 billion by 2020.

UNAIDS has set an agenda to Fast-Track the response to HIV by 2020 towards ending the AIDS epidemic as a public health threat by 2030. It will continue to work closely with its Cosponsors and partners to ensure that everyone, everywhere can fulfil their right to health and can access the health and social services they need.


In 2016 (*June 2017) an estimated:

*20.9 million [18.4 million–21.7 million] people were accessing antiretroviral therapy (in June 2017)

36.7 million [30.8 million–42.9 million] people globally were living with HIV

1.8 million [1.6 million–2.1 million] people became newly infected with HIV

1.0 million [830 000–1.2 million] people died from AIDS-related illnesses

UNAIDS

The Joint United Nations Programme on HIV/AIDS (UNAIDS) leads and inspires the world to achieve its shared vision of zero new HIV infections, zero discrimination and zero AIDS-related deaths. UNAIDS unites the efforts of 11 UN organizations—UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, UN Women, ILO, UNESCO, WHO and the World Bank—and works closely with global and national partners towards ending the AIDS epidemic by 2030 as part of the Sustainable Development Goals. Learn more at unaids.org and connect with us on Facebook, Twitter, Instagram and YouTube.

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New global commitment to end TB http://www.eatg.org/news/new-global-commitment-to-end-tb/ Tue, 21 Nov 2017 22:55:01 +0000 http://www.eatg.org/?post_type=news&p=6804 Over 120 national delegations that participated in the first Global Ministerial Conference on TB adopted the Moscow Declaration to End TB.

17 November 2017 | MOSCOW/GENEVA Today 75 ministers agreed to take urgent action to end tuberculosis (TB) by 2030. The announcement came at the first WHO Global Ministerial Conference on Ending Tuberculosis in the Sustainable Development Era: A Multisectoral Response, which brought together delegates from 114 countries in Moscow. President Vladimir Putin of the Russian Federation opened the Conference, together with Amina J Mohammed, UN Deputy Secretary General, and Dr Tedros Adhanom Ghebreyesus, WHO Director-General.

“Today marks a critical landmark in the fight to end TB,” said Dr Tedros. “It signals a long overdue global commitment to stop the death and suffering caused by this ancient killer.”

The Moscow Declaration to End TB is a promise to increase multisectoral action as well as track progress, and build accountability. It will also inform the first UN General Assembly High-Level Meeting on TB in 2018, which will seek further commitments from heads of state.

Global efforts to combat TB have saved an estimated 53 million lives since 2000 and reduced the TB mortality rate by 37%. However, progress in many countries has stalled, global targets are off-track, and persistent gaps remain in TB care and prevention.

As a result, TB still kills more people than any other infectious disease. There are major problems associated with antimicrobial resistance, and it is the leading killer of people with HIV.

“One of the main problems has been a lack of political will and inadequate investment in fighting TB,” added Dr Tedros. “Today’s declaration must go hand-in-hand with increased investment.”

The meeting was attended by ministers and country delegations, as well as representatives of civil society and international organizations, scientists, and researchers. More than 1000 participants took part in the two-day conference which resulted in collective commitment to ramp up action on four fronts:

  • Move rapidly to achieve universal health coverage by strengthening health systems and improving access to people-centered TB prevention and care, ensuring no one is left behind.
  • Mobilize sufficient and sustainable financing through increased domestic and international investments to close gaps in implementation and research.
  • Advance research and development of new tools to diagnose, treat, and prevent TB.
  • Build accountability through a framework to track and review progress on ending TB, including multisectoral approaches.

Ministers also promised to minimize the risk and spread of drug resistance and do more to engage people and communities affected by, and at risk of, TB.

The Russian Federation, host of the first Ministerial Conference to End TB, welcomed the Moscow Declaration. “Tuberculosis is a complex, multi-sectoral problem that requires a systemic and highly coordinated response to address the conditions which drive the disease,” said Professor Veronika Skvortsova, Minister of Health, Russian Federation. “The accountability framework we have agreed to develop marks a new beginning, and, with WHO’s support to coordinate and track progress, we expect the Moscow Declaration to lead us forward to the high-level meeting of the UN General Assembly in 2018.”

Access the WHO Global Ministerial Conference webpage here.

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TB: Governments given deadline to increase testing and treatment http://www.eatg.org/news/tb-governments-given-deadline-to-increase-testing-and-treatment/ Tue, 21 Nov 2017 22:50:55 +0000 http://www.eatg.org/?post_type=news&p=6798 Petition signed by more than 30,000 people from 120 countries presented to head of WHO and Ministers of Health.

Moscow/Geneva, 15 November 2017 – Ahead of the first-ever Global Ministerial Conference on Ending TB in Moscow, the international medical humanitarian organisation Médecins Sans Frontières (MSF) and the Stop TB Partnership called for countries with high burdens of tuberculosis (TB) to implement the latest international treatment and testing standards by World TB Day, 24 March 2018.

TB remains the world’s top infectious disease killer, with 1.7 million deaths in 2016. According to the latest World Health Organization (WHO) Global TB report, progress in diagnosing and treating all forms of TB is stalling in most countries: more than 4.1 million people with TB remained undiagnosed or unreported in 2016, and only one in five people with multidrug-resistant (MDR-TB) were started on treatment. Of those people, just over half were cured.

“Why do we continue to remain out of step when it comes to testing people for TB, when it’s the critical first step to treating this curable disease and preventing its spread?” said Dr. Francis Varaine, TB Medical Advisor at MSF. “Governments urgently need to step up, to stop people from needlessly dying of TB.”

According to a survey in the third edition of ‘Out of Step’, a joint report by MSF and the Stop TB Partnership that reviews TB policies and practices in 29 countries – which account for nearly three-quarters of the global TB burden – 40 percent of people with TB remain undiagnosed. Only seven of the countries* have made Xpert MTB/RIF, a rapid molecular test, widely available for diagnosing TB. Newer medicines and regimens for treating drug-resistant (DR-TB) have demonstrated better outcomes than today’s standard regimens, which cure just half of people with MDR-TB and only 28% of people with the even more deadly extensively drug-resistant (XDR-TB). Seventy-nine percent of countries surveyed include the newer drug bedaquiline in their national guidelines, and 62% include delamanid**, but globally, less than five percent of people who could have benefitted had access to these drugs in 2016.

This week, MSF and the Stop TB partnership released the report ‘Out of Step in Eastern Europe and Central Asia’ (EECA), presenting the results of an eight-country*** survey of national TB policies and practices. Among the countries surveyed, 75% have adopted a policy to use rapid molecular testing instead of older, slower testing methods, yet only half of those countries are actually using the test widely. An estimated 46,000 people with DR-TB in the EECA region went undiagnosed in 2015.

“Despite its deadly toll, most countries lag behind in implementing the existing and new tools that are available to tackle TB,” said Lucica Ditiu, Executive Director of the Stop TB Partnership. “The WHO Global Ministerial Conference is the first step for concrete, bold and measurable commitments by ministers of health towards a strong accountability framework for heads of state and governments during the UN High Level meeting on TB.”

At the Global Ministerial Conference this week, Mariam Avanesova, who was treated for MDR-TB in Armenia in 2010-2012 and represents TBpeople, the Eurasian network of people with TB experience, will hand over a petition to WHO’s Director-General, Dr. Tedros Ghebreyesus. The #StepUpforTB petition is an urgent call for health ministers in key TB-affected countries to get their TB policies and practices in line with international standards, as defined by WHO, including testing and treatment of TB and its drug-resistant forms. Initiated by MSF and the Stop TB partnership, the petition has been signed by more than 30,000 people from 120 countries united with people affected by TB.

“After being cured of MDR-TB, I decided to continue working in this area because I find it unacceptable that people are dying because either their diagnosis was too late and the drugs didn’t work, or they simply quit because the side effects from 20 tablets a day for two years were too much,” said Avanesova. “I really want to appeal to all governments to step up to make timely TB testing and treatment accessible to all people who need it. Urgent action on the ground is what I’m hoping to see come out of this conference.”

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* Armenia, Belarus, Brazil, Georgia, South Africa, Swaziland, and Zimbabwe

** WHO will carry out a review of emerging evidence on the use of delamanid in early 2018.

*** Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Russian Federation, Tajikistan and Ukraine

MSF is an independent international medical humanitarian organisation that delivers medical care to people affected by armed conflicts, epidemics, natural disasters and exclusion from health care. Founded in 1971, MSF has operations in over 60 countries today. MSF has been treating people with TB for 30 years. In 2016, MSF treated more than 20,000 people with TB, including 2,700 people with multi-drug-resistant TB (MDR-TB).

The Stop TB Partnership and its 1,600 partners are a collective force that is transforming the fight against TB in more than 110 countries.

Reading material:

Out of Step: TB policies in 29 countries, 3rd Ed. (2017)
http://stoptb.org/resources/publications/

Out of Step in Eastern Europe and Central Asia (EECA)
http://stoptb.org/assets/documents/outofstep/TB_Report_OutOfStepInEECA_ENG_2017.pdf

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Ending tuberculosis starts in Moscow http://www.eatg.org/news/ending-tuberculosis-starts-in-moscow/ Tue, 21 Nov 2017 22:45:35 +0000 http://www.eatg.org/?post_type=news&p=6802 A meeting of the world’s health ministers in Moscow this week could prove to be a pivotal moment on the road to ending tuberculosis.

November 16, 2017 – A meeting of the world’s health ministers in Moscow this week could prove to be a pivotal moment on the road to ending tuberculosis (TB).

A curable infectious disease, TB has recently dislodged HIV/AIDS as the world’s most deadly infectious disease, taking some 1.7 million lives and affecting another 10 million each year.

Clearly, the world is lagging in fighting tuberculosis, a largely curable disease that accounts for so many preventable deaths and infections.

In the case of  HIV/AIDS, early testing and a commitment to research resulting in a wide range of effective antiretroviral drugs have transformed the disease from a death sentence to a manageable condition. Some 19.5 million people are currently living with HIV and these efforts have saved millions of lives.

Rates of HIV infection have been declining in many countries for some years now with the notable exception of Eastern Europe and Central Asia, which is home to the fastest growing rates in the world. Russia and Ukraine account for the vast majority.

In Russia alone, it is estimated that over a million people are living with HIV compared to around 250 000 a decade ago.

The TB world is confronting the many challenges posed by the most common forms of the disease and the rapid growth of Multidrug Resistant TB. However, the highest rates of TB in the world are found in Eastern Europe and Central Asia.

Nine of the 12 countries in this region are on the World Health Organization’s global list of Multidrug Resistant Tuberculosis (MDR-TB) high burden countries. Two-thirds of the region’s MDR-TB burden is in the Russian Federation and Ukraine.

The statistics are frightening. Over 20 percent of all new cases coming for re- treatment – in Eastern Europe and Central Asia are Multidrug Resistant and the number of people with drug resistant TB in the region is increasing by five percent each year.

Across all 12 Eastern Europe and Central Asian countries, 30 percent of people estimated to have drug-resistant TB are not being diagnosed.

New drugs like Bedaquiline are only reaching three percent of all people living with MDR-TB in the region, and the number of new cases associated with an HIV infection is also rapidly increasing.

Under these circumstances, many observers see the World Health Organisation´s (WHO) noble deadline to eliminate TB by 2030 as precarious unless some major steps are taken to dramatically turn around decades of underinvestment in research and development.

Many strains of MDR TB are resistant to some — or nearly all — existing drugs. These strains kill 200,000 people annually. TB treatment is long, painful and in Eastern Europe and Central Asia results in a cure in only 50 percent of cases.

Treatment for a typical case of drug-sensitive TB lasts six months, while drug-resistant TB must be treated for nine to 24 months. The methods are outdated, using old drugs with severe side effects and curing only 54 percent of patients. If nothing changes, a projected 75 million people will die from TB by 2050.

Less than a third of funding required to develop new drugs is invested annually. The world’s only TB vaccine, now 90 years old, has failed to halt the global epidemic. TB vaccine research is grossly underfunded even though a vaccine for adolescents and adults would be the single most cost-effective solution to help end the epidemic. Today we continue to fight the world’s largest infectious-disease epidemic using antiquated diagnostics and treatment.

TB drug development lags far behind drug development for other priority pathogens, with only eight new antibiotics currently in development, compared to 42 antibiotics and biologicals in clinical development for other priority pathogens. Many leading pharmaceutical companies have withdrawn altogether from TB drug research.

Initiatives such as The Life Prize being announced this week could be the kind of breakthrough that will change the stagnant TB research and development status quo.

Formed by a coalition of global health organisations, The Life Prize’s aim is to develop a single affordable and accessible regimen that will cure all forms of TB within one month.

The Life Prize will incentivise and reward scientists to bring promising new TB drugs through the drug development pipeline.

Research funding initiatives of this kind will need sustained political commitment. It is promising that in its early days, the Life Prize has attracted strong support from the BRICS nations.

New agreements between Russian and international pharmaceutical companies to manufacture Multidrug TB drugs such as Delamanid and Bedaquiline are also encouraging.

But a potential new regime of TB science will also need to be matched by effective implementation on the ground.

That will mean some fundamental changes and reforms in the way that TB care is delivered in many parts of the world, including in Eastern Europe and Central Asia  where TB care remains largely hospital-based rather than decentralized to primary health care structures.

How to fund and implement those changes while also  driving the search for new diagnostic tools, drugs and vaccines that treat TB will be a focus of discussions this week in Moscow.

How seriously thereafter the world’s leaders take TB as a health crisis that needs prioritising we shall discover at the first ever United Nations High Level Meeting on TB, to be held in September 2018.

Eliminating TB will not be easy but neither is it impossible – history has shown that just as challenging global health crises have been overcome when political commitment and scientific innovation coalesce.

This week the TB community needs a strong dose of sensible talk leading into long term meaningful action. Eastern Europe, home to the world´s fastest growing HIV and MDR TB epidemics, seems a good place to start.

By José Luis Castro and Michel Kazatchkine
José Luis Castro
is Executive Director of The International Union Against Tuberculosis and Lung Disease (The Union)
Michel Kazatchkine
is the UN General Secretary´s Special Envoy on HIV/AIDS in Eastern Europe and Central Asia.

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EMA to relocate to Amsterdam, the Netherlands http://www.eatg.org/news/ema-to-relocate-to-amsterdam-the-netherlands/ Tue, 21 Nov 2017 22:30:10 +0000 http://www.eatg.org/?post_type=news&p=6809 Agency to begin working immediately with Dutch government to ensure successful move by end of March 2019

The European Medicines Agency (EMA) will relocate to Amsterdam in the Netherlands. This decision was taken today (November 20) by the EU 27 Member States in the margins of the General Affairs Council (Art. 50). The Agency now has just over 16 months to prepare for the move and take up its operations in Amsterdam on 30 March 2019 at the latest.

“We welcome today’s decision on the new location of EMA. Now that we finally know where our journey is taking us, we can take concrete actions for a successful move,” said EMA Executive Director Guido Rasi.

“Amsterdam ticks many of our boxes,” he continued. “It offers excellent connectivity and a building that can be shaped according to our needs. I am very grateful that the Member States took into account our requirements for business continuity and gave priority to the protection of public and animal health.

“Our internal surveys have shown that a large majority of EMA staff would be willing to move with the Agency to Amsterdam. However even in this case, our activities will be impacted and we need to plan for this now to avoid the creation of gaps in knowledge and expertise.”

EMA has to relocate due to the United Kingdom’s decision to withdraw from the EU. Amsterdam was one of 19 offers to host EMA submitted by the Member States at the end of July 2017. Today’s decision on EMA’s new location follows an assessment of the bids by the European Commission and EMA.

“My staff and I are very honoured that so many Member States showed an interest in hosting EMA,” Professor Rasi commented. “The huge effort invested by the bidding countries to put together their proposals is a reflection of the Agency’s important role in the protection of public and animal health and the stimulation of a vibrant and innovative pharmaceutical industry.”

The decision today marks the official start of a challenging joint relocation project that will have to be delivered within extremely tight timelines whereby the relocation has to be completed by 30 March 2019.

Effective collaboration between EMA and the Netherlands on the basis of the commitments made in its offer to host EMA is essential to ensure a successful move and the continuation of EMA’s operations with minimal disruption.

EMA and the Netherlands will kick start their collaboration by establishing a joint governance structure to steer and oversee the relocation project. Because of its important role to safeguard public and animal health in the EU, EMA is committed to giving stakeholders and the public full visibility of the relocation project. In early December, the Agency will make available a monitoring chart on its website that will allow to track the progress made.

Notes

  • EMA has been based in London, UK, since it was established in 1995. It currently employs nearly 900 staff members at its headquarters in Canary Wharf, London.
  • The relocation of EMA from London is a consequence of the UK’s withdrawal from the European Union. The Agency was not involved in the selection of the new location.

 

Read also:

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FDA approves first two-drug regimen for certain patients with HIV http://www.eatg.org/news/fda-approves-first-two-drug-regimen-for-certain-patients-with-hiv/ Tue, 21 Nov 2017 22:15:12 +0000 http://www.eatg.org/?post_type=news&p=6808 The U.S. Food and Drug Administration today approved Juluca, the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of three or more drugs included in standard HIV treatment. Juluca is a fixed-dose tablet containing two previously approved drugs (dolutegravir and rilpivirine) to treat adults with HIV-1 infections whose virus is currently suppressed on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.

“Limiting the number of drugs in any HIV treatment regimen can help reduce toxicity for patients,” said Debra Birnkrant, M.D., director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research.

HIV weakens a person’s immune system by destroying important cells that fight disease and infection. According to the Centers for Disease Control and Prevention, an estimated 1.1 million people in the United States are living with HIV, and the disease remains a significant cause of death for certain populations.

Juluca’s safety and efficacy in adults were evaluated in two clinical trials of 1,024 participants whose virus was suppressed on their current anti-HIV drugs. Participants were randomly assigned to continue their current anti-HIV drugs or to switch to Juluca. Results showed Juluca was effective in keeping the virus suppressed and comparable to those who continued their current anti-HIV drugs.

The most common side effects in patients taking Juluca were diarrhea and headache. Serious side effects include skin rash and allergic reactions, liver problems and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.

The FDA granted approval of Juluca to ViiV Healthcare.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The Agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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Statements from the European HIV-Hepatitis Testing Week Working Group http://www.eatg.org/news/statements-from-the-european-hiv-hepatitis-testing-week-working-group/ Sun, 19 Nov 2017 22:06:44 +0000 http://www.eatg.org/?post_type=news&p=6786 The European Testing Week Working Group has released two statements supporting safer and voluntary testing for key and most affected populations for HIV and hepatitis.

The first is a statement to all of Testing Week signatories to review the joint statement (available in 6 different languages) created by an informal alliance of NGOs and ensure access to effective, comprehensive, rights-based, safe, anonymous and voluntary HIV and Hepatitis testing for everyone in order to promote early diagnosis and linkage to care.

The Working Group released a second statement that encourages government bodies and policy makers to review the joint statement and consider supporting the outlined principles in legislation.

European HIV-Hepatitis Testing Week 2017 is taking place on 17-24 November.

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Webinar: EUPATI Online Toolbox http://www.eatg.org/news/webinar-eupati-online-toolbox/ Sun, 19 Nov 2017 22:05:20 +0000 http://www.eatg.org/?post_type=news&p=6788 Webinar: EUPATI Online Toolbox – resources about medicines research for patient advocates
Tuesday 21 November 17.00 – 18.00 CET

Please register here: https://attendee.gotowebinar.com/register/1320863496295663618
After registering, you will receive a confirmation email containing information about joining the webinar.

Moderator: Tamás Bereczky
Speakers: Matthew May (EUPATI project) and Giulio Maria Corbelli (EATG)

Background:
The EUPATI Online Toolbox (https://www.eupati.eu/) is targeted to patients advocates interested in understanding the benefits and practicalities of patient involvement in medicines research. The EUPATI Toolbox is now available in 8 languages (Dutch, English, French, German, Italian, Polish, Russian, Spanish) and contains also starter-kits adapted to prepare training and presentations on specific topics. The site also provides information and links to national platforms for patient advocates. This webinar demonstrates the use of the Toolbox and its different functionalities. Specific examples for patient advocates will be taken up.

Agenda:
17.00 – 17.10 The EUPATI project and the role of EATG in the project, introduction of speakers (Tamás)
17.10 – 17.30 Introduction to the Online Toolbox (Matthew)
17.30 – 17.50 Some concrete examples of the use of the Toolbox for EATG members (Giulio)
17.50 – 18.00 Q&A

For any questions, please contact Maria Dutarte at projects@eatg.org.

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First European community PrEP center opens in Barcelona http://www.eatg.org/news/the-first-european-community-center-dedicated-to-the-hivaids-prevention-pill-opens-in-barcelona/ Sun, 19 Nov 2017 22:04:38 +0000 http://www.eatg.org/?post_type=news&p=6781 The first European community center dedicated to the HIV/AIDS prevention pill opens in Barcelona

BCN PrEP·Point follows up with individuals who take the medication “on their own accord” and aims to help research its effects

15 November 2017

PrEP – the preventive HIV/AIDS pill – may not be approved in Spain, yet, but the BCN PrEP·Point center, dedicated to the medication, is already a reality. Opened by the BCN CheckPoint organization, the objective of this Barcelona center is to advance any work possible and provide information on this medication, even before it becomes accessible in Spain.

This is why it will be working at first with those who are taking the pill “on their own accord,” stated Ferran Pujol, director of the BCN CheckPoint, in order to achieve adherence to the treatment. The benefits of the medication would translate in a decrease of infection, which currently sits at 2 per day in Catalonia. Pujol stated that it was necessary to begin working with a tool that would prevent more contagion.

A smaller sample size

It’s calculated that around 100 people will participate in the study promoted by PreEP·Point. With the resulting data, it will then be possible to study the behavior of participants and the effect this has on the number of infections.

The target number set by the Department of Health is set at some 10,000 individuals. Yet, according to the BCN Checkpoint director, this number is too high. Indeed, he stressed that the study sample size must be smaller to verify the effects of the drug, as not all transgender women or men who have intercourse with other men wish to undergo the treatment.

Both Pujol and the medical director of the center, Pep Coll, agreed that 1,700 people would be sufficient, describing previous studies that were done with a size of less than 4,000, and achieving a 90% fall in infection. To obtain this reduction, according to Pujol, “it’s not necessary to immunize the whole population.” Still, he noted that infection is for life, and could cost up to €150,000 in treatment.

“PrEP allows the normalization of not only intercourse – but also, of human interactions with other people”
Ferran Pujol · Director of BCN CheckPoint

The “four pillars” to “reduce the incidence of HIV in the gay community”

The HIV and AIDS health crisis has devastated the world for the better part of 30 years, and the LGBTQ community has been hit particularly hard. BCN CheckPoint, set up in 2006, was the first center in all of Spain “to introduce the rapid HIV test in a non-medical setting.” The community-based center is dedicated to “the detection of HIV and other sexually transmitted infections, targeted at gay men, other men who have sex with men, and transgender women.” As a further part of its philosophy, BCN CheckPoint states that it “approaches sexuality openly, without fears, moral judgments or prejudice.”

In an earlier September press release, the BCN CheckPoint detailed the “four pillars” of its “global strategy to significantly reduce the incidence of HIV in the gay community.” These are, as they explained, increased frequency of HIV testing, access to antiretroviral treatment for those who have been diagnosed, screening and treatment for other sexually transmitted infections, and the PrEP medication.

A controversial treatment

PrEP stands for Pre-exposure Prophylaxis. It’s administered in the form of a pill to be taken daily and works by reducing the chances of infection for individuals at very high risk of contracting HIV. Combining two different drugs – tenofovir and emtricitabine – it prevents the virus from multiplying. When taken properly and as indicated, the medication can reduce the possibility of infection by 90% in sexual encounters.

As many with many preventative measures, there has been some controversy around the release and use of the PrEP drug. The debate stems from the idea that, if one feels safe, one might engage in riskier behavior – in this case, higher-risk sexual intercourse. Yet, a study published in the Journal of the International AIDS society suggests that when taken correctly, the use of PrEP is not only safe – it’s effective, too.

“Normalizing” human interactions

To compare PrEP with other strategies, Pujol noted that BCN CheckPoint’s actions have already yielded a slight decrease in infections due to early diagnosis. It’s estimated that the incidence of HIV in Catalonia, concentrated in the LGBTQ community and in urban centers, affects 0.02% of the general population, but among transgender women or men who have sex with other men, the number is at 2.3%. For those responsible for PrEP· Point, the goal is to reach the same levels of incidence between the two groups. Pujol further considers it “negligence” to let two people become infected every day.

Users of the PrEP treatment, explained by Ferran Pujol, have stated that taking the medication allows them to “normalize” not only intercourse but also human interactions with other people.” The director of BCN CheckPoint notes that after been “30 years” of living in the “shadow of suspicion,” PrEP is allowing this to finally change.

Living with HIV/AIDS

This comes just in time to preface the 14th ‘Jornades VIH’ on November 20The event is dedicated to the “promotion and quality of life for people with HIV/AIDS,” where individuals who live with the condition can meet and share their stories, as well as attend conferences about the latest advances in cures.

Watch a short video here.

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Second-generation vaginal films address issues with current HIV prevention methods http://www.eatg.org/news/second-generation-vaginal-films-address-issues-with-current-hiv-prevention-methods/ Sun, 19 Nov 2017 22:00:26 +0000 http://www.eatg.org/?post_type=news&p=6797 Sexual transmission is the main method of human immunodeficiency virus type 1 (HIV-1) infection in women. The effectiveness of topical microbicides for HIV-1 prevention can be inconsistent and insufficient, which are associated with low adherence rates and/or product misuse. To address these difficulties, researchers presenting at the 2017 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition designed extended release vaginal films which could be effective in HIV prevention for up to seven days.

The team from the University of Pittsburgh School of Pharmacy and Magee-Womens Research Institute developed extended release topical microbicide products in the form of vaginal films. These films were tested in a nonhuman primate model at the University of Washington. The films use a combination of a modified natural polymer and functional biopolymer to prolong the time the dosage form remains in the vagina and delivers the antiretroviral drug.

“Vaginal films are desirable because they are convenient, non-messy, low-cost dosage forms which can be discreetly used,” said researcher Jing Li at the University of Pittsburgh School of Pharmacy. “Since multiple applications of vaginal films can be undesirable, we developed an extended release film platform which does not require frequent administration.”

The study, “Design of Advanced Mucoadhesive Coitally-Independent Vaginal Films for HIV Prevention,” was conducted with five nonhuman primates using the second-generation thiomer PLA-CL film. Results demonstrated compatibility between the films and the cervical tissue as well as enhanced mucoadhesiveness and retention. The biodegradable film platform is similar to a mouthwash strip in that it dissolves in body fluids.

In Phase I studies, the first-generation films which provided on-demand drug delivery, were demonstrated to be safe, acceptable, and delivered sufficient amounts of drug to the vagina for protection from HIV infection.

Li added, “We believe that this more convenient dosing platform will be one that women are more likely to use in their day-to-day lives with the hope that this could decrease infection rates in this highly susceptible population.”

The researchers next step will be putting highly potent antiretroviral drugs into the second-generation film and testing its ability to prevent HIV infection in human tissue.

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About AAPS: The American Association of Pharmaceutical Scientists (AAPS) is a professional, scientific organization of approximately 9,000 members employed in academia, industry, government, and other research institutes worldwide. Founded in 1986, AAPS advances the capacity of pharmaceutical scientists to develop products and therapies that improve global health. Visit http://www.aaps.org and follow us on Facebook and Twitter @AAPSComms. The official Twitter hashtag for the meeting is: #AAPS2017.

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Developing a new vaccination strategy against AIDS http://www.eatg.org/news/developing-a-new-vaccination-strategy-against-aids/ Sun, 19 Nov 2017 21:58:34 +0000 http://www.eatg.org/?post_type=news&p=6790 The type of vaccine administered and the activation of the body’s own immune cells influence the vaccine protection

According to the WHO, there are currently more than 36 million people infected with the human immunodeficiency virus (HIV) and a further 2.4 million become infected every year. Despite all the medical treatment success against the virus, an efficacious vaccine is of utmost importance. Infection researchers from the German Primate Center (DPZ) – Leibniz Institute for Primate Research have in cooperation with international colleagues tested a new vaccination strategy against the HIV-related simian immunodeficiency virus (SIV) in rhesus monkeys. For this, the researchers used a vaccine that consisted of two components. The monkeys were immunized subcutaneously, orally and intramuscularly with a time delay and in alternating order. The scientists were able to show that the type of booster vaccine, orally and intramuscularly, as well as the order of the vaccine components, influenced the activation of the immune system. These represent vital factors in the long-term prevention of a SIV infection. Since SIV and HIV mainly replicate in the body’s own activated CD4+ T helper cells that are critical for the immune defense, it is crucial that their level remains relatively low even after vaccination. In order to achieve sustained protective immunity against AIDS, a vaccination strategy inducing a balanced immune response without an increase of CD4+ T helper cells must be developed (Journal of Virology).

There are many reasons for the lack of a vaccine against HIV infection. In contrast to conventional vaccines, the (active) agent against HIV must trigger an immune response strong enough to make sure that no single cell will be infected, otherwise the virus will be permanently integrated into the genome of the cells. This is not necessary with other vaccines since most viruses are not firmly anchored to the genome. For this, a vaccine response more rapid than the spread of the virus and one that can stop damage to the cells is sufficient.

Another hurdle for a vaccine against AIDS is the immune system itself. In order for the body’s immune system to trigger an optimal immune response, CD4+ T helper cells are needed. The dilemma for vaccine research is that these cells are also the target cells for an infection with HIV or SIV. In an international cooperation with Italian and Austrian partners, an American research group and German experts from Erlangen, Bochum and Kiel, Ulrike Sauermann and Christiane Stahl-Hennig, scientists from the Unit of Infection Models at the German Primate Center, have tested a vaccination approach that takes these critical factors into account.

The researchers administered a potential vaccine consisting of two components to twelve rhesus monkeys that served as an animal model for the human HIV infection. The administration of a compound vaccine is referred to as a prime-boost vaccination. In the initial step, all monkeys were treated with genetically modified SIV, which infected the host cells but was unable to replicate in the body. This procedure serves as an “initial stimulant” of the immune system (priming). The monkeys were then divided into two groups, where they then received the second vaccination component consisting of two different viral vectors via different routes.

The non-pathogenic vectors serve as gene shuttles to transport components of SIV, such as envelope proteins, into the target cells. This second step increases the immune response (boost). In the first step, six monkeys received an adenovirus gene shuttle, which was administered orally as a spray. In the second step they received an intramuscular injection with a gene shuttle from the fowlpox virus. For the other six monkeys, the scientists reversed the process. In this group, first the fowlpox vector was administered orally, followed by the adenovirus vector as an injection. Following this, the monkeys had weekly intervals of exposure to low doses of SIV, which triggers an AIDS-like disease. This process continued until almost all the monkeys were infected.

“We observed that the virus in all vaccinated animals initially replicated less than in the control group,” Ulrike Sauermann, first author of the study, summarized the results. “This shows that the vaccine induced a protective response in the immunized monkeys. In the second group that was first treated with the fowlpox vector and afterwards with the adenovirus vector, the likelihood of an infection was reduced by about 70 percent, compared to only a 12 percent reduction in the first group. In addition, the CD4+ T helper cells were less activated in the second group.”

The data show that the order and type of administration (oral spray or injection) of the vaccines may affect the activation of the immune system and may have a long lasting effect that affects subsequent immunizations as well as the susceptibility to infection. It is therefore important to find a balance between the T helper cell response and the remaining immune responses. An excessive activation of CD4+ T helper cells can otherwise reverse the protective immune response.

“Results from a former AIDS vaccine study have shown that in a worst case scenario, immunization against HIV could enhance infection,” says Christiane Stahl-Hennig, who designed the project in cooperation with the former DPZ employee Sieghart Sopper. “Even though a comparable monkey vaccination strategy previously failed, the study was nevertheless carried out in humans. In order to identify and avoid possible risks that could arise from vaccination against AIDS, it is essential to carefully plan and execute animal experiments in pre-clinical studies. We do believe that we have found an effective component for a compound vaccine. The immunization with SIV components in a fowlpox vector appears to be safe and promising. In the follow-up experiments, our aim is the further improvement of the booster immunization in order to achieve an even higher efficiency and protection rate.”

Original publication

Sauermann, U, Radaelli, A, Stolte-Leeb, N, Raue, K, Bissa, M, Zanotto, C, Frawczak, M, Tenbusch, M, Überla, K, Keele, BF, de Guilio Morghen, C, Sopper, S, Stahl-Hennig, C (2017): Vector order determines protection against pathogenic simian immunodeficiency virus infection in a triple component vaccine by balancing CD4+ and CD8+ T-cell responses. Journal of Virology. doi: 10.1128/JVI.01120-17

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No change in cognitive function or brain structure in people taking effective HIV treatment for 2 years http://www.eatg.org/news/no-change-in-cognitive-function-or-brain-structure-in-people-taking-effective-hiv-treatment-for-2-years/ Sun, 19 Nov 2017 17:54:07 +0000 http://www.eatg.org/?post_type=news&p=6779 People with HIV taking antiretroviral treatment who had undetectable viral load did not suffer any loss of cognitive function or brain volume during a two-year period when compared with their HIV-negative peers, but did have lower cognitive function and brain volume at the start of the study, suggesting that changes occur before effective treatment starts, according to the findings of a study published this week in the journal JAMA Neurology.

Although a mild loss of cognitive function can be detected in up to 40% of people living with HIV it is unclear if people with HIV taking effective antiretroviral therapy will suffer a progressive decline in cognitive function, or if any deterioration in cognitive function is a result of physical changes in the brain.

To answer these questions, researchers from McGill University, Montreal (Canada), and Washington University, St Louis (USA) designed a study to follow people living with HIV for two years and compare their cognitive function and brain structure with a demographically similar HIV-negative control group.

They recruited 23 women and 25 men living with HIV, with an average age of 47 years and 13.3 years of education. Just over two-thirds were African American (69%). People were excluded from the study if they had any history of opportunistic infections affecting the brain, traumatic brain injury, psychiatric disorder or substance use disorder. The control group consisted of 16 women and 15 men with an average of 51 years and 14.5 years of education. Fifty-two per cent were African American.

All people with HIV were taking antiretroviral treatment and had fully suppressed viral load. They had been infected with HIV for a median of 13.5 years, had a current median CD4 cell count of 630 cells/mm3 and a median nadir CD4 count of 190 cells/mm3.

Cognitive function was assessed using eight tests recommended for evaluation of HIV-associated neurocognitive disorders.

Changes in the brain were assessed using magnetic resonance imaging (MRI). These scans of the brain measured changes in the volume of the brain and its various components (white matter, grey matter, cerebrospinal fluid) and changes in the thickness of the cerebral cortex.

Participants were tested and scanned twice, at an average interval of 2.1 years.

After adjusting for age, sex and educational level, people living with HIV had significantly lower scores in six of the eight tests of neuropsychological function at baseline. There was no relationship between CD4 cell count, nadir CD4 cell count or duration of infection and neuropsychological scores.

During the follow-up period, HIV-positive study participants showed no deterioration in test scores.

Differences between the two groups in the volume of several regions of the brain were detected at baseline, as well as significantly lower cortical thickness. Again, no significant changes in the brain were detected during the follow-up period.

The study authors argue that the lack of relationship between CD4 cell counts, nadir CD4 cell counts or duration of infection and most brain changes suggests that any neurocognitive deficit becomes established in the early phase of HIV infection. More work is needed, they say, to confirm the hypothesis that early treatment – within a year of infection – might reduce the prevalence of HIV-associated neurocognitive disorders (HAND).

There was no relationship between exposure to antiretroviral drugs with greater penetration into the central nervous system and neuropsychological function or brain volume, although the number of different regimens taken by study participants was too small to determine if any regimen was protective or neurotoxic.

The investigators say that the study population was large enough to detect clinically meaningful changes and that their findings mirror those of other studies that used different methods to assess changes in cognitive function in people on antiretroviral treatment.

An important limitation of their study, say the investigators, is that they can’t rule out that smaller brain volume and cognitive deficits could be partly explained by cardiovascular disease, and specifically by microvascular in the brain.

By Keith Alcorn

Reference

 

Read also:

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Long-term data do not support raltegravir as second-line HIV therapy http://www.eatg.org/news/long-term-data-do-not-support-raltegravir-as-second-line-hiv-therapy/ Sun, 19 Nov 2017 17:52:52 +0000 http://www.eatg.org/?post_type=news&p=6795 A second-line HIV regimen containing the integrase inhibitor raltegravir failed to meet its primary endpoint of noninferiority against standard second-line treatment with nucleoside reverse-transcriptase inhibitors, or NRTIs, according to 144-week data from the EARNEST trial.

James G. Hakim, FRCP, of the University of Zimbabwe Clinical Research Center, and colleagues said their findings have “important implications for second-line therapy in the public health approach” to HIV.

“The good longer term outcomes with the combination of a protease inhibitor (in this case lopinavir) with two NRTIs provides support for this regimen as the WHO-recommended preferred second-line combination,” they wrote in The Lancet Infectious Diseases.

Although WHO recommends NRTIs as part of standard second-line therapy, the world health agency’s 2016 guidelines include raltegravir as an alternative option. To determine whether the drug offered any additional benefit over NRTIs, Hakim and colleagues compared the outcomes of 1,277 patients no longer responding to first-line ART in sub-Saharan Africa who were randomly assigned to a regimen containing:

400 mg of lopinavir plus 100 mg of ritonavir twice daily and two to three clinician-selected NRTIs (n = 426);

400 mg of raltegravir and protease inhibitor twice daily (n = 433); or

protease inhibitor monotherapy with an initial 12-week induction of raltegravir and reintroduction of combination ART after 96 weeks (n = 418).

The researchers hypothesized that the protease inhibitor plus raltegravir regimen — two new active drug classes — would be superior to a regimen containing NRTIs. The primary outcome was a viral load less than 400 copies/mL at week 144.

At the end of the study period, the proportion of patients with viral loads less than 400 copies/mL was 86% in the protease inhibitor plus NRTI group vs. 81% in the protease inhibitor plus raltegravir group. Although the raltegravir-containing regimen did not meet the 10% noninferiority margin, it was not significantly inferior to the NRTI-containing regimen. In the protease inhibitor monotherapy group, 78% of patients had less than 400 copies/mL.

There were no significant differences in the incidence of serious adverse events, grade 3 or 4 adverse events or events that led to treatment modifications, according to the researchers. In the protease inhibitor plus raltegravir group, 7% of patients had resistance to raltegravir and 3% had resistance to lopinavir. In the control group, 3% of patients had resistance to one or more NRTIs and 2% had resistance to lopinavir. Among those who received protease inhibitor monotherapy, 11% had resistance to lopinavir.

“Taking into account the higher cost of raltegravir, the absence of clear advantages of protease inhibitor plus raltegravir seen in any trial and the failure to show noninferiority consistently across all analyses after 144 weeks of treatment in this trial suggest that there is no compelling reason for national programs to adopt this combination as the standardized second-line therapy in the public health approach to [ART],” Hakim and colleagues wrote.

The researchers suggested that dolutegravir — an integrase strand transfer inhibitor with a high genetic barrier to resistance and longer half-life than raltegravir — may be more suitable for second-line therapy in resource-limited settings.

In a related editorial, Andrew M. Hill, PhD, senior visiting Research Fellow in the department of translational medicine at the University of Liverpool, and Francois Venter, MD, FCP, deputy executive director of the Wits Reproductive Health and HIV Institute, University of the Witwatersrand, noted that several countries are beginning to transition both first- and second-line treatment regimens to include dolutegravir. This could be an “important step” toward simplifying treatment and lowering costs, according to the authors. They estimated that fixed-dose combinations of tenofovir/lamivudine/dolutegravir average $75 per person-year in low-income countries, which is much less than the price of current first-line therapy.

“The results from EARNEST and other similar clinical trials suggest that NRTIs will retain efficacy in second-line treatment when used with protease inhibitors,” they wrote. “We now need to ensure that this protective effect also allows newer drugs such as dolutegravir to be used with recycled NRTIs in second-line treatment.”

Raltegravir is sold under the brand name Isentress (Merck). Lopinavir/ritonavir is sold under the brand name Kaletra (AbbVie).

Hakim JG, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30630-8.
Hill AM, Venter F. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30631-X.

By Stephanie Viguers

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GeoVax HIV clinical trials update http://www.eatg.org/news/geovax-hiv-clinical-trials-update/ Sun, 19 Nov 2017 17:52:47 +0000 http://www.eatg.org/?post_type=news&p=6793 Participant enrollment completed for HVTN 114 trial

15 November 2017: GeoVax Labs, Inc. (OTCQB: GOVX), a biotechnology company developing human vaccines, today announced that the HIV Vaccine Trials Network (HVTN) has closed enrollment for the phase 1 human clinical trial evaluating late boosts of GeoVax’s preventive vaccine (GOVX-B11) for clade B HIV. The trial, designated HVTN 114, is being conducted by the HVTN and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

HVTN 114 began in January 2017, enrolling individuals who previously participated in the HVTN 205 Phase 2a trial of the GOVX-B11 vaccine, which concluded in 2012. HVTN 114 tests the ability of late boosts (additional vaccinations) to increase the antibody responses elicited by the GeoVax vaccine regimen. These “late boosts” consist of the GeoVax MVA62B vaccine with or without a gp120 protein vaccine. The gp120 protein, AIDSVAX® B/E, is the same protein used to boost immune responses in the partially protective RV144 trial in Thailand, and is being used in HVTN 114 to assess the effect of adding a protein vaccine to GOVX-B11. Participants in

HVTN 114 receive either (a) another MVA62B boost, (b) a combined boost of MVA62B and AIDSVAX® B/E, or (c) AIDSVAX® B/E alone. Meanwhile, newer proteins are being manufactured using current Good Manufacturing Practices (cGMP) for use with GOVX-B11 in future clinical trials.

Harriet L. Robinson, Ph.D., director of GeoVax’s HIV vaccine program, commented, “We are pleased with the progress HVTN has made in the conduct of HVTN 114 and look forward to completion of the immunizations and analysis of the results. Information from this trial will contribute to the design of clinical trials testing GOVX-B11 in combination with the new gp120 proteins that are currently being prepared.”

GeoVax has designed GOVX-B11 for use against the clade B subtype of HIV prevalent in the Americas, Australia, Japan and Western Europe. GOVX-B11 consists of two vaccine components – a recombinant DNA vaccine (pGA2/JS7) and a recombinant live MVA (modified vaccinia Ankara) virus vaccine (MVA/HIV62B), both expressing Gag, protease, reverse transcriptase and Env (gp120/gp41) proteins from HIV-1. The DNA vaccine is intended to prime a person’s immune response, and the MVA/HIV62B to boost the primed response. Both the DNA and MVA vaccines produce non-infectious virus-like particles in the cells of the vaccinated person. The HVTN has tested various doses and regimens of GOVX-B11 in trials involving a total of approximately 500 participants where it has been shown to be safe and well-tolerated. AIDSVAX® B/E is supplied by Global Solutions for Infectious Diseases (GSID).

About HVTN

The HVTN is the world’s largest publicly funded multi-disciplinary international collaboration facilitating the development of vaccines to prevent HIV/AIDS. The HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and immunogenicity to testing vaccine efficacy. Primary funding for the HVTN is provided by the NIAID. HVTN trial sites are located at leading research institutions in 27 cities on four continents. The Network’s headquarters are at the Fred Hutchinson Cancer Research Center in Seattle, Washington. For more information, go to www.hvtn.org.

About GeoVax

GeoVax Labs, Inc., is a clinical-stage biotechnology company developing human vaccines against infectious diseases using its MVA-VLP vaccine platforms. The Company’s HIV vaccine for the clade B epidemic in the Americas, Australia, Japan and Europe is advancing in human trials conducted by the HVTN. Preclinical programs are focused on preventive vaccines for Zika virus, hemorrhagic fever viruses (Ebola, Sudan, Marburg, and Lassa), and malaria, as well as therapeutic vaccines for HIV, chronic Hepatitis B infections and cancers. GeoVax’s vaccine platform supports in vivo production of non-infectious VLPs from the cells of the very person receiving the vaccine, mimicking a natural infection and effectively stimulating both the humoral and cellular arms of the immune system to recognize, prevent, and control the target infection. For more information, visit www.geovax.com.

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Theratechnologies announces FDA decision to extend the ibalizumab review period http://www.eatg.org/news/theratechnologies-announces-fda-decision-to-extend-the-ibalizumab-review-period/ Sun, 19 Nov 2017 17:50:07 +0000 http://www.eatg.org/?post_type=news&p=6783 Theratechnologies Inc. announced that it was notified by its partner, TaiMed Biologics, Inc., that the U.S. Food and Drug Administration will extend its review of the Biologics License Application for ibalizumab. In a notice received today by TaiMed from the FDA, the Prescription Drug User Fee Act target action date has been extended to April 3, 2018.

Read the full press release here.

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Global Fund appoints Peter Sands as Executive Director http://www.eatg.org/news/global-fund-appoints-peter-sands-as-executive-director/ Sun, 19 Nov 2017 17:45:40 +0000 http://www.eatg.org/?post_type=news&p=6784 GENEVA, 14 November 2017 – The Board of the Global Fund to Fight AIDS, Tuberculosis and Malaria today appointed a new Executive Director: Peter Sands [ download in English | Français ] , a former chief executive of Standard Chartered Bank who after a distinguished career in banking immersed himself in a range of global public health projects.

Sands, who is currently Chairman of the World Bank’s International Working Group on Financing Pandemic Preparedness, is also a research fellow at the Harvard Global Health Institute and the Mossavar Rahmani Center for Business and Government at Harvard’s Kennedy School, where he works on research projects in global health and financial regulation.

“Peter Sands brings exceptional management and finance experience, and a heart for global health,” said Aida Kurtović, Board Chair of the Global Fund. “At a time when we face complex challenges, his ability to mobilize resources while managing transformational change is exactly what we need. We expect him to take the Global Fund to the next level.”

Sands served as Chief Executive Officer of Standard Chartered PLC from 2006 to 2015, having joined the bank in 2002 as Group Finance Director. Under his leadership, Standard Chartered successfully navigated the turbulence of the global financial crisis in 2007-2009, continuing to support clients and counterparties throughout the worst of the financial stresses and without drawing on government support of any kind.

Sands led Standard Chartered’s transformation into one of the world’s leading international banks, reinforcing its focus on emerging markets and driving the development of world-class product, risk management and technology capabilities, underpinned by a highly collaborative culture. During Sands’ tenure as CEO, Standard Chartered focused its corporate responsibility initiatives on health issues, including avoidable blindness, AIDS and malaria. Sands served on the board of the Global Business Coalition on AIDS, Tuberculosis and Malaria and was Lead Non-Executive Director on the board of the United Kingdom’s Department of Health.

After stepping down from the bank in 2015, Sands deployed his skills and experience in international finance on global health. Sands served as Chairman of the U.S. National Academy of Medicine’s Commission on a Global Health Risk Framework for the Future, which published the influential report on pandemics entitled The Neglected Dimension of Global Security: a Framework to Counter Infectious Disease Outbreaks. Sands is also serving on the U.S. National Academy of Science’s Forum on Microbial Threats and Committee on Ensuring Access to Affordable Drugs. Sands has published articles on global health and epidemics in various peer-reviewed journals.

“I am deeply honored to join this extraordinary partnership,” Sands said. “Infectious diseases today represent one of the most serious risks facing humankind. If we work together to mobilize funds, build strong health systems and establish effective community responses we will be able to end epidemics, promote prosperity and increase our global health security.”

Born in the United Kingdom, Sands was educated in Malaysia, the UK, Canada and the U.S. He began his career in the UK’s Foreign Office and then joined McKinsey & Company, where he worked for 13 years in the London office, advising clients in the financial services and telecommunications sectors.

Sands graduated from Brasenose College, Oxford University with a First Class degree in Politics, Philosophy and Economics. He also received a Master’s in Public Administration from Harvard University, where he was a Harkness Fellow.

As new Executive Director, Sands will oversee and guide the implementation of the Global Fund’s 2017-2022 strategy, designed to maximize impact against HIV, TB and malaria and build resilient and sustainable systems for health.

The Global Fund is a 21st-century partnership organization designed to accelerate the end of AIDS, tuberculosis and malaria as epidemics. Founded in 2002, the Global Fund is a partnership between governments, civil society, the private sector and people affected by the diseases.

The Global Fund raises and invests nearly US$4 billion a year to support programs run by local experts in countries and communities most in need. The Global Fund has been consistently rated as one of the most effective and transparent organizations in the development sector.

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Aidspan publishes two new issues of ‘Global Fund Observer’ http://www.eatg.org/news/aidspan-publishes-two-new-issue-of-global-fund-observer/ Sun, 19 Nov 2017 17:43:50 +0000 http://www.eatg.org/?post_type=news&p=6791 Aidspan, an independent watchdog of the Global Fund to Fight AIDS, Tuberculosis and Malaria, published Issue 324 and Issue 325 of the “Global Fund Observer.” The latter includes articles on various topics, including primary decisions made at the Global Fund Board meeting; the Board’s approval of a $312 million operating expenses budget for 2018; and the approval of the 2017-2022 Key Performance Indicator Framework, which provides the Global Fund with a set of targets against which to measure its work.

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Reduced risk of hepatic steatosis in HIV/HCV coinfection with cannabis use http://www.eatg.org/news/reduced-risk-of-hepatic-steatosis-in-hivhcv-coinfection-with-cannabis-use/ Sun, 19 Nov 2017 16:51:12 +0000 http://www.eatg.org/?post_type=news&p=6796 Daily cannabis use was shown to be associated with a reduced risk for liver steatosis among individuals co-infected with HIV and hepatitis C, according to the results of a recent study published in the Journal of Viral Hepatitis.

In this analysis of patients from a French cohort of people co-infected with HIV and hepatitis C, the association of steatosis and cannabis use was evaluated. Ultrasound examination was used to determine the presence of steatosis, and self-administered questionnaires collected sociobehavioral data, including cannabis use frequency.

A total of 40.1% (n=336/838) of study participants had liver steatosis. Most participants did not use or only occasionally used cannabis (74.7%), followed by daily use (14.0%) or regular use (11.7%).

Daily cannabis use was more common among patients who were negative for steatosis compared with those who were positive (16.1% vs 10.7%; P =.08). After adjusting for body mass index, hazardous alcohol consumption, and current or lifetime use of lamivudine or zidovudine, daily cannabis use was correlated with a lower risk for steatosis (adjusted odds ratio [OR] 0.64; 95% CI, 0.42-0.99; P =.046).

Other factors associated with liver steatosis included high body mass index (adjusted OR 1.93; P =.02), current or lifetime exposure for lamivudine or zidovudine (adjusted OR 1.51; P =.01), and hazardous alcohol consumption (adjusted OR 1.73; P =.03).

In an interview with Infectious Disease Advisor, Patrizia Carrieri, epidemiologist at the French National Institute of Health and Medical Research INSERM UMR 912, Marseilles, France, and senior author on the study, concluded that, “although we hypothesize that the association between lower steatosis risk and cannabis use may be attributable to the anti-inflammatory properties of cannabis, we must remain cautious about causality.”

By Jessica Martin

Reference

Nordmann S, Vilotitch A, Roux P, et al; ANRS CO13 HEPAVIH Study Group. Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus co-infected patients (ANRS CO13-HEPAVIH) [published online October 6, 2017]. J Viral Hepat. doi: 10.1111/jvh.12797

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DAAs produce cure rates in HCV/HIV co-infection similar to monoinfection http://www.eatg.org/news/daas-produce-cure-rates-in-hcvhiv-co-infection-similar-to-monoinfection/ Sun, 19 Nov 2017 16:49:24 +0000 http://www.eatg.org/?post_type=news&p=6794 Using direct-acting antiviral therapies demonstrated similarly high rates of sustained virologic response for hepatitis C virus infection in patients with and without HIV infection as compared with rates for HCV mono-infected patients, according to findings published in Hepatology.

“Because of low [sustained virologic response] rates associated with interferon-based therapies, the accelerated progression of HCV related liver disease, and barriers to receiving treatment, the [FDA] identified those infected with HIV and HCV co-infection as being a specific population with unmet medical needs,” Cameron Sikavi, third-year resident from the department of medicine at Harbor-University of California at Los Angeles Medical Center, and colleagues wrote. “With the advent of [DAA] therapies, HCV treatment has resulted in higher cure rates with short treatment duration in comparison to pegylated-interferon and ribavirin based therapies, in addition to improved safety and tolerability profiles.”

Prior research has shown that DAA treatment can improve life expectancy and SVR rates. Using clinical databases, researchers performed a systematic review of the treatment for chronic HCV infection in patients infected with HIV to determine whether using DAA agents addresses an unmet medical need in these patients and results in similar SVR rates as HCV mono-infected persons. In their review, the investigators included studies dated between January 2004 and July 2017, searching the keywords “hepatitis C,” “HIV,” “coinfection” and “direct-acting antiviral.”

Patients with HCV and HIV coinfection treated with interferon-based treatments had substantially lower SVR rates compared with rates seen in HCV mono-infected patients. Mono-infected persons who started taking DAA agents had similar SVR rates as compared with co-infected persons, with SVR greater than 93%. In comparison to interferon-based regimens, DAA medications have been shown to have improved the safety, efficacy and tolerability in both co-infected and mono-infected patients. Sikavi and colleagues also note that physicians should be aware of antiretroviral medications for HIV before starting a patient on HCV treatment, and of comorbidities that may impact SVR.

“Given the success of DAA therapy, it is imperative that future research be aimed at identifying programs and interventions that reduce the risk of reinfection among this population,” Sikavi and colleagues wrote. “Clinicians must remain vigilant, especially with regard to identifying drug-drug interactions, negative predictors or SVR, and barriers to care. By doing so, the improvements in SVR rates afforded with DAAs can address an unmet medical need among the coinfected population, with significant clinical implications.”

Sikavi C, et al. Hepatology. 2017doi:10.1002/hep.29642.

By Savannah Demko

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FDA approves hepatitis C drugs label updates http://www.eatg.org/news/fda-approves-hepatitis-c-drugs-label-updates/ Sun, 19 Nov 2017 16:47:00 +0000 http://www.eatg.org/?post_type=news&p=6780 FDA recently approved changes to the labels of:

  • Sovaldi (sofosbuvir), Harvoni (ledipasvir and sofosbuvir), Epclusa (sofosbuvir and velpatasvir) and Vosevi (sofosbuvir, velpatasvir, and voxilaprevir). The approved changes are detailed here.
  • VIEKIRA PAK™ (ombitasvir, paritaprevir, and ritonavir tablets, 12.5 mg/75 mg/50 mg; dasabuvir tablets, 250 mg), VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) and TECHNIVIE (ombitasvir, paritaprevir, and ritonavir). The approved changes are detailed here.
  • OLYSIO (simeprevir), DAKLINZA (daclatasvir) and ZEPATIER (grazoprevir/elbasvir). The approved changes are detailed here.
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Open letter to the Romanian MoH to focus on TB http://www.eatg.org/news/open-letter-to-the-romanian-moh-to-focus-on-tb/ Thu, 16 Nov 2017 19:34:07 +0000 http://www.eatg.org/?post_type=news&p=6776 The Romanian Health Observatory, supported by the Romanian Angel Appeal Foundation (RAA) under the Global Fund programme, has published “The Crisis of Anti-TB Medicines in Romania”, a comprehensive and evidence-based report and long-term sustainable solutions for the TB drugs situation in our country. The report is endorsed by the Romanian Stop TB Partnership.

The Report states that “Out of the 28 investigated TB medicines mentioned as essential or necessary for the treatment of Tuberculosis and drug-resistant tuberculosis by the World Health Organization or by the Methodological Guidelines for Implementing the National Program for the Prevention and Control of Tuberculosis in Romania, 15 essential drugs are reported to be unavailable or have disruptions in supply caused by existing legislative barriers in Romania. Other 3 drugs recommended in international guidelines, but considered to have alternatives, are missing from Romania.”

Despite the slight fall in TB incidence, Romania still has the highest number of new TB cases every year in the EU. It also is an upper-middle income country, which will make it ineligible for international donors in the near future.

Since 2007, full-course drug regiments for the treatment of MDR/XDR-TB have been procured by RAA through GDF mechanism, with funding from the Global Fund and Norway Grants. These drugs supported the NTP to provide adequate non-interrupted treatment to over 2,000 MDR/XDR TB patients. In addition, with the support of the Global Fund, a WHO Technical Assistance Mission was organized by RAA in 2016 to assess the situation and formulate recommendations for resolving the crisis. Until now, the Romanian State has made no significant progress in this regard.

We urge the Romanian Government to take immediate action in order to be able to procure the full regimens for both TB and MDR/XDR-TB patients, from domestic funds.

We have designed an open letter for the Romanian Prime Minister and the Minister of Health we want to send and publish this week. Please find attached the open letter, the Executive Summary and the full report, in English.

This letter has also been endorsed by EATG: TB Romania Open Letter_with signatures

]]> Join MSF and Stop TB Partnership in asking countries to #StepUpforTB http://www.eatg.org/news/join-msf-and-stop-tb-partnership-in-asking-countries-to-stepupfortb/ Sat, 11 Nov 2017 22:59:32 +0000 http://www.eatg.org/?post_type=news&p=6743 Join Médecins Sans Frontières (MSF) and the Stop TB Partnership in a call to action to #StepUpforTB by signing and sharing a petition by 14 November 2017. The petition will be delivered at the Global Ministerial Conference on Ending TB to be held on 16-17 November 2017 in Moscow, Russia. Sign the petition here!      

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Vital microbicides may soon be out of reach http://www.eatg.org/news/vital-microbicides-may-soon-be-out-of-reach/ Sat, 11 Nov 2017 22:55:34 +0000 http://www.eatg.org/?post_type=news&p=6762 Whether, when, and how microbicide development proceeds depends on the U.S government, and the federal Division of AIDS has suggested this development may no longer be a priority. It’s wrong.

The first proven microbicide to prevent HIV may be ready for market by the end of the decade. That’s the good news. The bad news: Although there are numerous candidate microbicides in the research pipeline, this first one could end up being the only one to become publicly available. That’s because of a push to eliminate funding for research of these vital tools. The public has until November 30 to comment on such a move. More on that later.

For over 25 years, women have been calling for an HIV prevention tool that is woman-initiated, easy to use, undetectable during sex and, ideally, comes in both contraceptive and non-contraceptive forms. Research to develop such products, called microbicides, started in 1992.

Twenty-five years later, a vaginal ring, replaced monthly, is now undergoing regulatory review by the European Medicines Agency, the first microbicide to make it to this point. The International Partnership for Microbicides plans to submit it to the South African Health Products Regulatory Authority (South Africa’s equivalent of the FDA) in early 2018, followed later by submissions to other national regulatory authorities in sub-Saharan Africa. If the ring is approved, the soonest it is currently projected to be available in some countries is late 2019. It will be the realization of a dream almost three decades in the making.

Like the contraceptive NuvaRing, this microbicidal ring is a hollow silicone device—but loaded with dapivirine, an anti-HIV drug, that is released gradually over the course of a month. In clinical trials, the ring reduced new HIV infections by 56 percent among women who used it consistently as instructed.

The chance to cut one’s HIV risk in half is big news, indeed, in areas where most of the 25- to 29-year-olds with HIV (two-thirds) are women, and where only about half of all adults between 25-49 years old report using condoms regularly. Researchers estimate that this vaginal ring, alone, could “avert at least a million HIV infections [globally] over the next 20 years.”

Oral pre-exposure prophylaxis (PrEP), a pill to prevent HIV, is a new prevention strategy that offers much higher levels (over 90 percent) of protection if taken daily. A recent demonstration project among young women in South Africa, however, showed that even while getting reminders to take a pill daily, only 57 percent of participants had detectable levels of the prevention drug in their blood at week 12, and 38 percent by week 24. This suggests that the higher efficacy of the pills can be offset by inconsistent use when daily adherence is required.

The dapivirine ring is just the first of several microbicide candidates under development. Researchers are now testing the feasibility of longer-lasting, multi-purpose rings loaded with both an anti-HIV drug and a contraceptive, thus preventing both HIV and pregnancy simultaneously for up to three months. One-time use, fast-dissolving vaginal films and tablet inserts (to be inserted before sex) are also being tested.

Several “behaviorally congruent” rectal microbicide products are also in development. These products are formulated to look and feel like the douches and lubricants that people often use before or during anal sex—but have the advantage of containing anti-HIV drugs. Thus, they should fit comfortably into common sexual behaviors while also providing protection to the user and her/his partner. 

Why Would Microbicide Development Stop Now?

Whether, when, and how microbicide development proceeds depends on the U.S government simply because it has provided almost all the funding so far to develop HIV prevention tools, including PrEP, microbicides, and the (still elusive) HIV vaccine. This funding has been allocated by the Division of AIDS (DAIDS) at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health (NIH).

Between 2000-2016, for example, over $3 billion was spent globally on microbicides research and four times that amount—more than $12 billion—on vaccine development. Almost all of this money (93 percent of the vaccines funding and 84 percent of the microbicides funding in 2016, for example) came from DAIDS.

Now, however, the government is looking to reduce funding for all kinds of important public health research, including for HIV and AIDS. DAIDS Director Carl Dieffenbach announced earlier this year that he will be leading the NIH’s effort to “refine the HIV research enterprise” by prioritizing funding for HIV prevention products that are both long-acting (work in the body for six months or longer) and systemic (affecting the whole body). Vaccines, long-term injectable PrEP, and implants meet this definition. But microbicides do not.

Microbicides are instead localized, only affecting the part of the body that needs protection; reversible, because drug levels do not remain in the body long after use; short-acting, designed to be used only at the time of sex (the vaginal ring is an exception to this); and user-controlled, meaning not injected or inserted by a medical provider.

One of DAIDS’ arguments against microbicides is that “it has not been demonstrated that the most vulnerable users would choose or adhere to these products.” This is based on the results of a few microbicide gel trials and two ring trials, in which ring use among some participants was lower than expected. Additional research is pending to see if the low rates of ring use among younger women were motivated by physical, social, or behavioral factors.

Two “open-label” studies are also underway to assess ongoing interest in the product. Once the effectiveness of a new product has been proven, an open label trial is done to see how participants feel about using it. Typically, uptake and adherence is significantly greater in open-label trials because participants know they are all getting the real product and not being randomly assigned to either the real drug or the placebo (or fake drug), as occurs in the effectiveness trial.

The question of ring acceptability among younger women, in particular, is also a matter of ongoing study. Between 2014-2016, a U.S. study enrolled 96 sexually active girls (ages 15-17) in six cities and found that almost all (95 percent) participants described the ring as easy to use. Blood tests done to confirm product use among the study participants found the preventive drug in 87 percent of the participants blood samples. Another trial in Africa is also planned to look specifically at how African adolescent girls and young women (16-21) feel about the ring.

Despite the mixed data on young women’s willingness to use the microbicidal ring, Dr. Dieffenbach, a biophysicist, maintains that DAIDS funding should only be allocated to developing prevention tools that are both long-lasting and systemic. Advocates see this decision as resulting in the defunding of microbicide research altogether. The only other potential funder for the field would be private, corporate interests. Unfortunately, the available evidence demonstrates that that this expectation is not at all realistic.

At its highest level (in 2006-07), commercial investment comprised 2 percent of all funding for microbicide research, and development and came from small biotech companies, not pharmaceutical corporations. By 2016, commercial interests were providing 0.2 percent of all resources for microbicide development. Without public support, and specifically without DAIDS funding, microbicide research and development will likely stall. This will waste 25 years of labor, amassed expertise, and investment that have brought the field to this present cusp of success, as well as the opportunity to put HIV prevention into women’s hands.

DAIDS’ focus on long-lasting methods overlooks the fact that effective microbicides are right around the corner and no injectable PrEP (which would likely require six clinic visits per year) or HIV vaccines have proven levels of effectiveness. Further, it ignores the great lesson of contraception: that different people want different methods. When people have a range of birth control choices (pills, implants, rings, injections, intrauterine devices, and so on) available to them, the number of unintended pregnancies goes down. One size does not fit all, especially in terms of personal protection. We can’t end AIDS by ignoring that lesson.

Between Now and November 30: Take Action

DAIDS has provided an opportunity for the public (in the United States and internationally) to submit comments between now and November 30. These comments go straight to DAIDS and they make a difference!

To enter your comments to DAIDS about microbicide funding, go to: https://www.niaid.nih.gov/forms/refining-hiv-research-enterprise-response-form

Here are some points to keep in mind:

  1. The United States has been, by far, the world’s strongest funder for microbicides research to date. If that stops in the next funding cycle, the chance to finish development of microbicides that could save millions of lives will be lost.
  2. Men who have sex with men in a wide range of countries and young women, especially those in southern Africa, are two key populations at very high risk of HIV contraction. If we can reduce their vulnerability to HIV, we may be able to turn the tide of AIDS. Both populations have expressed the desire for microbicides and a willingness to use them. Their needs are immediate, urgent, and ongoing.
  3. A multi-purpose vaginal ring is already in development that would provide women with contraception and HIV protection—an enormous benefit, especially for young women. The United States must not stop now and miss the chance to put these kinds of tools into women’s hands!
  4. Several rectal microbicide products are now being tested for their feasibility and safety. With so much money and time already invested, it would be financially wasteful not to finish testing these candidates to find out if one or more of them works for rectal protection.

You can also sign on to an international community letter to DAIDS on this issue by clicking on this link. Signers (organizations and individuals) from all nations are welcome!

The level of alarm about this change in direction has even roused Congress members’ attention. Rep. Jan Schakowsky (D-IL) has initiated a “Dear Colleague” letter inviting her colleagues to join her in signing to, “Support Microbicides as an NIH and NIAID Research Priority.” Please speak out with us on this urgent issue. Together, we can be heard.

For more information on this issue, please visit http://rectalmicrobicides.org/save-microbicide-research-and-development/.

By Anna Forbes

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Russia’s methadone ban is fueling an HIV epidemic in Crimea http://www.eatg.org/news/russias-methadone-ban-is-fueling-an-hiv-epidemic-in-crimea/ Sat, 11 Nov 2017 22:50:20 +0000 http://www.eatg.org/?post_type=news&p=6755 Georgy’s drug addiction started when he was just 15.

It began with the painkillers doctors gave him after he fractured his hip. But tension at home made it difficult to stop and the habit spiraled beyond his control.

“When my prescription ran out,” he says, “I started to buy soft drugs on the street. By the time I was 21, I was hooked on heroin.” Soon, he was making his own heroin at home.

In 2008, eight years into his addiction, doctors told him he had one year left to live and Georgy realized he needed help. He began a drug substitution therapy called OAT to safely wean himself off drugs.

At that point, Crimea, where Georgy lived, was still part of Ukraine and substitution therapy (OAT) was legal. But when Russia annexed Crimea in March 2014, the peninsula’s new leadership announced the therapy would be banned.

By May that year, more than 800 drug users who had been receiving OAT, including Georgy, found themselves cut off from treatment. Now local and international rights groups say the ban is fueling a resurgent HIV epidemic with fatal consequences.

“When I started OAT, my life became manageable,” Georgy, now 33, says. “I could work, I gained self-confidence and I stopped associating with criminals. If it weren’t for OAT, I wouldn’t be alive.”

‘Painful situation’

Backed by the World Health Organization (WHO) and used in over 60 countries, OAT replaces street narcotics with methadone or buprenorphine, which are less potent and longer lasting. It is widely considered to be one of the most effective methods of reducing opioid misuse and preventing HIV.

Centers where patients received daily treatment and had access to social and counseling services operated in cities across Crimea for nine years before the annexation.

The impact of the ban on Crimeans has been dramatic, local and international rights groups say. According to United Nations statistics, up to 120 patients have died from suicide, overdoses, or complications related to HIV and tuberculosis, as a result of being cut off from medication to suppress the viruses.

Another 14,000 Crimeans, who were covered by HIV prevention services, like needle exchanges, have also been cut off from treatment, according to the International HIV/AIDS Alliance in Ukraine, an NGO dedicated to issues around HIV and AIDS.

“Most OAT patients have reverted to street drugs like ‘krokodil’ and some have been put in prison,” Pavlo Skala, Associate Director at International HIV/AIDS Alliance in Ukraine, told The Moscow Times.

“Many HIV-positive patients lost touch with the health care system and came back to hospitals in a terminal phase,” he says. “The situation is painful.”

Western consensus

Ajay Manhapara, a research scientist at Yale University, argues that quitting heroin without OAT is “dangerous.”

Krokodil, the cheap heroin substitute that rights groups say is sweeping Crimea, is a deadly black-market drug. Poorly made, it can cause giant abscesses in the skin, exposing the flesh to viruses and paralyzing muscles. According to HIV/AIDS Alliance in Ukraine, its use is now rapidly increasing.

“Dependent drug users in an OAT program decrease their risk of mortality by two-thirds compared with those who try to give it up by themselves,” Manhapara said.

Russian officials, however, remain opposed, and Health Ministry officials have denied the deaths are related to the methadone ban.

In 2011, Viktor Ivanov, the head of Russia’s Federal Anti-Narcotics Agency, said “there have been no clinical trials to prove the effectiveness of the method.”

He claimed that OAT “helped to kill drug users” and that people who participated in the program were 10 times more likely to die compared to those who did not engage in the “inhumane scheme.”

In a 2014 speech in Crimea, Ivanov derided OAT as serving the interests of Western pharmaceutical companies.

“This is an incredible line of propaganda,” says Michel Kazatchkine, UN Special Envoy for AIDS in Eastern Europe and Central Asia. “The evidence is compelling, overwhelming and comprehensive.”

“The discontinuation of OAT in Crimea is a blatant example of health policy being hijacked for political ends rather than being led by evidence.”

Growing epidemic

Moreover, Kazatchkine says, the OAT ban is fueling Russia and Ukraine’s growing HIV epidemic.

Over the past decade HIV infections in Russia have soared from 170,000 in 2004 to 1.5 million last year, according to a joint European Center for Disease Prevention and Control (ECDP) and WHO report. Drug users are most at risk.

Russia accounts for nearly two-thirds of all new HIV infections in the European region, the report found. After Russia, Ukraine has the second largest HIV epidemic, with 240,000 people living with HIV.

Research by International HIV/AIDS Alliance in Ukraine shows that infection rates among younger drug users had decreased more than fivefold between 2007 and 2013 after OAT was introduced.

“OAT and other harm-reduction measures had begun to reverse Ukraine’s HIV/AIDS epidemic, which was mainly the result of injection drug users,” Skala says.

According to Chief Doctor of the Crimean State Center for Prevention and Control of AIDS Alexander Nemkin, 1,417 newly diagnosed cases of HIV were recorded in Crimea in the first nine months of 2016 — and 25 percent of those cases were the result of drug injection.

The figures mark an overall increase of 10 to 12 percent in HIV cases compared with the previous year.

Independent NGOs are working to counter the increased risk of HIV in Ukraine and Russia. But the Russian government has added some of the groups to its list of “foreign agents,” a stigma which can lead to fines and is leading groups to drop foreign funding.

That list includes ARF, the only HIV-focused organization offering free needle exchange in Moscow. “We do carry out our work using foreign funding, but this is not because we want to work this way,” ARF says in online statement in June 2016.

“Over the last few years, we applied for presidential grants four times so that our work could be funded from Russian sources, but our projects were never financed,” the statement says.

“Russia has never supported HIV prevention services among people who inject drugs, which is why the number of new infections both among this group as well as the general population is dramatically increasing,” says Andrei Klepikov, the Executive Director of the International HIV/AIDS Alliance in Ukraine in March 2014.

“We should not let 14,000 Ukrainian drug users be taken hostage in this way, cutting them off from life-saving medical services,” he says.

About 60 patients, including Georgy, were able to leave Crimea for treatment in the Ukrainian capital Kiev. With the support of the International HIV/AIDS Alliance they received housing, food and social support too. But leaving Crimea isn’t an option for most patients who either can’t afford to travel costs or have family commitments.

Georgy says he knows he was one of the lucky OAT patients. One of his friends, he says, died from an overdose when he couldn’t access treatment.

“I don’t know what happened to the rest. I haven’t heard from them since I left.”

By Madeline Roache

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A modest increase in U.S. investment to fight HIV/AIDS in sub-Saharan Africa could prevent 22 million new HIV infections by 2032 http://www.eatg.org/news/a-modest-increase-in-u-s-investment-to-fight-hivaids-in-sub-saharan-africa-could-prevent-22-million-new-hiv-infections-by-2032/ Sat, 11 Nov 2017 22:48:43 +0000 http://www.eatg.org/?post_type=news&p=6758 Analysis examines historical and potential impact of U.S. global health funding in region bearing heavy HIV/AIDS burden

NEW YORK, Nov. 10, 2017 – A new analysis shows that nearly 5 million lives in sub-Saharan Africa have been saved since 2003 as a result of U.S. investments in the global HIV/AIDS response. According to the analysis, if investment in global AIDS programs is increased by 10 percent, up to 22 million new HIV infections and 2.3 million deaths could be averted in the region by 2032.

Researchers at Imperial College London, amfAR, The Foundation for AIDS Research, and Friends of the Global Fight Against AIDS, Tuberculosis and Malaria examined the historical impact of U.S. global health investments and the implications of budget cuts in sub-Saharan Africa, the region that is home to 70 percent of all people living with HIV. Their findings are published online in the November 28 edition of the journal AIDS.

“As the leader in the global HIV/AIDS response, the United States has been instrumental in significantly reducing millions of AIDS-related deaths and preventing millions of HIV infections in Africa,” said Jessica B. McGillen, a research associate from the Department of Infectious Disease Epidemiology at Imperial College London and the lead author. “This analysis underscores the dramatic consequences of the U.S. not funding or reducing its commitment to fighting the epidemic.”

While U.S. investment in global health programs constitutes a tiny proportion of the nation’s federal spending budget — just a quarter of one percent – the U.S. is the largest donor to the global fight against HIV/AIDS through the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). PEPFAR is among the most successful global health programs in history and is currently supporting 11.5 million people on lifesaving antiretroviral treatment (ART). The Global Fund is the world’s largest public-private funder for HIV, tuberculosis and malaria, and along with PEPFAR has been vital in funding treatment delivery, supporting HIV testing services, and scaling up HIV prevention services. Global Fund-supported programs have saved more than 22 million lives to date.

The Administration proposed cuts that would have decreased global AIDS funding for PEPFAR by $800 million and for the Global Fund by $225 million in Fiscal Year 2018, representing reductions of 18 and 17 percent, respectively.

A World Without PEPFAR and the Global Fund

The authors used a mathematical model of HIV transmission to evaluate the impact of U.S. support for HIV programs across sub-Saharan Africa. They sought to determine how the HIV epidemic might have progressed if the U.S. had failed to invest and how the epidemic is likely to evolve under several future U.S. funding scenarios, and to explore the impact of a shift away from key at-risk populations.

Using financial data to assess the impact of lost PEPFAR and the Global Fund contributions if the programs had never been established, the authors found that AIDS mortality rates would have continued to increase instead of dropping in the mid-2000s, resulting in 3.7 million more HIV infections by the end of 2016 and nearly 5 million more lives lost to the epidemic.

From 2017 onward, if current numbers of people on treatment are maintained without any program expansion, as has been proposed by the Administration, the model indicated that 25.7 million new HIV infections and nearly 4.4 million AIDS deaths could occur by 2032.

A stepped-up response with a 10 percent increase in U.S. funding for PEPFAR and the Global Fund, coupled with more ambitious domestic HIV spending by African countries, and a focus on optimizing resource allocation, including targeting key at-risk populations, would enable 83 percent of adults with HIV to be virally suppressed on treatment, and avert more than 22 million new HIV infections and 2.3 million AIDS-related deaths over a 15-year period, relative to no expansion of the programs.

“Deaths from HIV-related causes have been halved since 2005, and more than half of all people living with HIV are on life-saving treatment, but the epidemic is far from over,” said Alana Sharp, a policy associate with amfAR and one of the authors. “We hope this informs funding and allocation decisions for global health, because without the political will and appropriate investments, we won’t be able to do what is needed to end the epidemic.”

“PEPFAR and the Global Fund work together at the country level to drive down HIV mortality and incidence, and their exceptional results deserve continued U.S. investment,” said Chris Collins, President of Friends of the Global Fight. “Yet the fight against HIV remains underfinanced. Building on the impact we’ve seen, it’s time to accelerate the effort to save lives and end the AIDS epidemic.”

Click here for more information on the impact of U.S. investments on PEPFAR.

# # #

About amfAR
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested more than $480 million in its programs and has awarded grants to more than 3,300 research teams worldwide.

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World Antibiotic Awareness Week 13-19 November to draw attention to global AMR threat http://www.eatg.org/news/world-antibiotic-awareness-week-13-19-november-to-draw-attention-to-global-amr-threat/ Sat, 11 Nov 2017 22:45:10 +0000 http://www.eatg.org/?post_type=news&p=6764 World Antibiotic Awareness Week will take place next week from 13-19 November, shining a spotlight on the growing crisis of antimicrobial resistance (AMR). The first descriptions of infectious diseases becoming resistant to the antimicrobial treatments available were in 1948 and were for drugs used to treat tuberculosis (TB).

Although major gains have been made in medical R&D, the problem of drug-resistant TB (DR-TB) has only worsened. In 2016, there were an estimated 600,000 new cases of DR-TB. It is predicted that by 2050, DR-TB will lead to 2.5 million deaths annually, which would be a quarter of antimicrobial resistance (AMR) deaths.

“AMR is one of the most critical challenges the world faces. Strengthening the response to TB is a cornerstone in the fight against AMR.” said José Luis Castro, Executive Director of The Union.

World Antibiotic Awareness Week coincides with the World Health Organization’s (WHO) global political meeting of ministers in Moscow, Russia, on “Ending TB in the Sustainable Development Era: A Multisectoral Response”. The meeting aims to accelerate implementation of the WHO End TB Strategy, with immediate action addressing the DR-TB crisis, and will then inform the UN General Assembly High-Level Meeting (HLM) on TB in 2018.

The Russian Federation is one of the three countries in the world with the highest number of DR-TB cases, with those three countries (India, China and Russia) bearing more than half of the global burden. The incidence of DR-TB in Russia continues to increase, meaning it is crucial to the success of the international effort to end TB.

The WHO describes antibiotic resistance as one of the biggest threats to global health, food security, and development today. Earlier this year, the WHO’s Priority Pathogen Report, highlighted DR-TB as a priority for research and development in the battle against AMR. The report went on to highlight five key reasons why TB is a global priority for research and development.

Echoing this concern, the WHO Director General, Dr. Tedros, has said, “We cannot underestimate this crisis and we must do better to identify, track and manage these drug-resistant TB cases as part of our AMR efforts.”

Dr Paula I Fujiwara, Scientific Director of The Union said: “We need new and innovative approaches to research and development if we’re to solve the crisis of antimicrobial resistance. We look forward to working further with global leaders to accelerate progress against TB and AMR.”

As part of our work to combat this growing threat, The Union is working with partners on The Life Prize, a new way to unite researchers and incentivise new TB research and development funding.

Grania Brigden, Project Lead for The Life Prize said: “The Life Prize (formerly known as the 3P Project) aims to overcome the barriers to TB treatment development to ensure a healthy TB drug pipeline and ensuring that promising candidates are developed as combination regimens and are affordable and accessible to all those in need.”

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Eliminating viral hepatitis: time to match visions with action http://www.eatg.org/news/eliminating-viral-hepatitis-time-to-match-visions-with-action/ Sat, 11 Nov 2017 22:43:28 +0000 http://www.eatg.org/?post_type=news&p=6750 Viral hepatitis caused an estimated 1·4 million deaths in 2015—similar to tuberculosis and more than either HIV or malaria, yet historically these diseases have received insufficient attention from donors and policy makers. In May, 2016, the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis, 2016–20, which aims to eliminate viral hepatitis as a major public health threat by 2030. The strategy set global targets to reduce new viral hepatitis infections by 90% and to reduce deaths due to viral hepatitis by 65%, focusing mainly on hepatitis B virus (HBV) and hepatitis C virus (HCV), which are responsible for most of the global burden. Last week, politicians, policy makers, researchers, and members of civil society met in São Paulo, Brazil, at the World Hepatitis Summit to take stock, with new data indicating that only a handful of countries are set to meet the 2030 targets.

Practices associated with increased risks of contracting HBV and HCV have contributed to stigma and discrimination against patients, especially prisoners and people who inject drugs. Prevention of both diseases involves reducing the risks of exposure to the viruses, and, for hepatitis B, vaccination. Acute HBV and HCV infection tend to be asymptomatic; however, chronic infections can lead to cirrhosis and hepatocellular carcinoma. Antiviral treatment for hepatitis B is not curative, but can slow disease progression and improve survival, whereas direct-acting antiviral (DAA) therapy for hepatitis C can cure around 95% of cases.

New data from WHO, released at the summit, showed the number of people who were newly treated for hepatitis C increased from 1·1 million in 2015 to 1·76 million in 2016. Likewise, 2·8 million people began treatment for hepatitis B in 2016, up from 1·7 million in 2015. Despite these improvements, data from the Polaris Observatory indicated that although 82 countries now have viral hepatitis plans, only nine (Australia, Brazil, Egypt, Georgia, Germany, Iceland, Japan, the Netherlands, and Qatar) are on track to reach their 2030 elimination goals for hepatitis C. Globally, a major challenge is diagnosis, with many countries “running out” of patients with hepatitis C to treat, according to the World Hepatitis Alliance. Indeed, new Polaris data indicate that just 20% of people with HCV have been diagnosed, ranging from around 44% in high-income countries to 9% in low-income countries.

The price of DAAs, especially in high-income countries, is a barrier to providing effective treatment, with the list price of a 12-week course of sofosbuvir and daclatasvir ranging from US$78 in India to $77 000 in the UK and around $96 000 in the USA. Like many high-income countries, Australia initially restricted access to DAAs. But in March, 2016, following the implementation of a risk-sharing agreement with pharmaceutical companies, Australia initiated universal access. On a background of high diagnosis rates, this led to the treatment of over 30 000 patients in 2016. Challenges for the USA include the opioid crisis, which has caused some states to see steep increases in new HCV infections through injection drug use. Stretched prison budgets mean that although an estimated one in six prisoners has hepatitis C, few are treated.

Children represent a particular challenge. The Polaris Observatory estimates that 52 million children were living with viral hepatitis in 2016—4 million with HCV and 48 million with HBV. Whereas new HBV infections are declining in children owing to vaccine use, new HCV infections are on the rise. Mother-to-child transmission was the main source of paediatric HCV infection, pointing to the need for comprehensive prevention programmes for women of childbearing age. Worryingly, treatment options are limited, with DAAs not recommended for pregnant women or children younger than 12 years. Writing in a recent Series paper for The Lancet Gastroenterology & Hepatology, Wendy Spearman and colleagues argue that prevention of mother-to-child transmission through screening and treatment is a key priority for HBV elimination in sub-Saharan Africa.

Several innovations could accelerate progress towards 2030 targets, including improved point-of-care diagnostics, establishing better treatment options for young children and pregnant women with hepatitis C, developing a functional cure for hepatitis B, improving access to generic DAAs, raising awareness and combating stigma, and developing sustainable financing models as part of progress towards universal health coverage. Yet, fundamentally, the tools needed to move towards elimination targets already exist—an effective vaccine for hepatitis B and a curative treatment for hepatitis C. What is needed now more than anything else is the political will to scale up prevention, diagnosis, and treatment programmes.

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Dynavax announces FDA approval of HEPLISAV-B(TM) for prevention of hepatitis B in adults http://www.eatg.org/news/dynavax-announces-fda-approval-of-heplisav-btm-for-prevention-of-hepatitis-b-in-adults/ Sat, 11 Nov 2017 22:07:14 +0000 http://www.eatg.org/?post_type=news&p=6752 First and only two-dose vaccine in United States for prevention of hepatitis B in adults
First new hepatitis B vaccine in United States in more than 25 years

BERKELEY, CA — 11/09/17 — Dynavax Technologies Corporation (NASDAQ: DVAX) today announced that the U.S. Food and Drug Administration (FDA) has approved HEPLISAV-B [Hepatitis B Vaccine, Recombinant (Adjuvanted)] for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older. HEPLISAV-B is the first new hepatitis B vaccine in the United States in more than 25 years and the only two-dose hepatitis B vaccine for adults.

Hepatitis B is an extremely infectious and potentially deadly virus affecting a wide range of adults in the United States. There is no cure for hepatitis B, and infections are on the rise. In 2015, new cases of acute hepatitis B increased by more than 20 percent nationally.(i) Hepatitis B can be prevented through effective vaccination. Current hepatitis B vaccines require three shots over a six-month period, however, almost half of adults fail to complete the series within one year.(ii)

“Prevention of hepatitis B in adults through vaccination is more important than ever given the increase in the rate of infections,” said William Schaffner, M.D., professor of Preventive Medicine, Vanderbilt University Medical Center. “Too many at-risk adults remain unprotected against this virus. A two-dose schedule with higher rates of protection, along with other strategies, may help us move closer to the goal of eliminating hepatitis B as a public health problem in the United States.”

The approval of HEPLISAV-B was based on data from three Phase 3 non-inferiority trials of nearly 10,000 adult participants who received HEPLISAV-B. The pivotal studies compared HEPLISAV-B administered in two doses over one month to Engerix-B administered in three doses over a six-month schedule. Results from the largest Phase 3 trial, which included 6,665 participants, showed that HEPLISAV-B demonstrated a statistically significantly higher rate of protection of 95% compared with 81% for Engerix-B. In a subgroup analysis of 961 participants with Type 2 diabetes, HEPLISAV-B demonstrated a statistically significantly higher rate of protection of 90% compared to 65% for Engerix-B. Across the three clinical trials, the most common local reaction was injection site pain (23% to 39%). The most common systemic reactions were fatigue (11% to 17%) and headache (8% to 17%).

“HEPLISAV-B is the first FDA-approved product for Dynavax and demonstrates our ability to develop innovative products and progress them from discovery to commercialization,” said Eddie Gray, chief executive officer of Dynavax. “We would like to thank the many study participants and clinical trial investigators who contributed to the development of HEPLISAV-B. We expect that it will become an essential tool in the public health community’s fight to prevent hepatitis B, and we look forward to making HEPLISAV-B available to clinicians and their adult patients.”

Dynavax expects to commercially launch HEPLISAV-B in the United States in the first quarter of 2018. In preparation for launch, Dynavax has been building commercial infrastructure and optimizing manufacturing processes to meet anticipated demand.

About Hepatitis B

Hepatitis B is a viral disease of the liver that can become chronic and lead to cirrhosis, liver cancer and death. The hepatitis B virus is 50 to 100 times more infectious than HIV,(iii) and transmission is on the rise. There is no cure for hepatitis B, but effective vaccination can prevent the disease. In adults, hepatitis B is spread through contact with infected blood and through unprotected sex with an infected person. The CDC recommends vaccination for those at high risk for infection due to their jobs, lifestyle, living situations and travel to certain areas.(iv) Because people with diabetes are particularly vulnerable to infection, the CDC recommends vaccination for adults age 19 to 59 with diabetes as soon as possible after their diagnosis, and for people age 60 and older with diabetes at their physician’s discretion.(v) Approximately 20 million U.S. adults have diabetes, and 1.5 million new cases of diabetes are diagnosed each year.(vi)

About HEPLISAV-B

HEPLISAV-B is an adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary Toll-like Receptor (TLR) 9 agonist to enhance the immune response. Dynavax has worldwide commercial rights to HEPLISAV-B.

Indication and Use
HEPLISAV-B is indicated for active immunization against infection caused by all known subtypes of hepatitis B virus. HEPLISAV-B is approved for use in adults 18 years of age and older.

Important Safety Information (ISI)
Do not administer HEPLISAV-B to individuals with a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B vaccine or to any component of HEPLISAV-B, including yeast.

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of HEPLISAV-B.

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to HEPLISAV-B.

Hepatitis B has a long incubation period. HEPLISAV-B may not prevent hepatitis B infection in individuals who have an unrecognized hepatitis B infection at the time of vaccine administration.

The most common patient reported adverse reactions reported within 7 days of vaccination were injection site pain (23% to 39%), fatigue (11% to 17%) and headache (8% to 17%).

For full Prescribing Information for HEPLISAV-B, click here.

About Dynavax

Dynavax is a commercial-stage biopharmaceutical company focused on leveraging the power of the body’s innate and adaptive immune responses through toll-like receptor (TLR) stimulation. Dynavax discovers and develops novel vaccines and immuno-oncology therapeutics. The Company’s first commercial product, HEPLISAV-B, a hepatitis B vaccine for adults, is approved in the United States. Dynavax’s lead immunotherapy product, SD-101, is an investigational cancer immunotherapeutic currently being evaluated in Phase 1/2 studies and its second cancer immunotherapeutic, DV281, is in Phase 1 development. For more information, visit www.dynavax.com.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding the commercial launch and manufacturing of HEPLISAV-B. These statements are subject to a number of risks and uncertainties that could cause actual results to differ materially, including whether the company will be able to build the commercial infrastructure required to launch HEPLISAV-B; whether we will launch HEPLISAV-B in the first quarter of 2018; whether we will be able to ramp up manufacturing activities to meet demand for HEPLISAV-B; whether the CDC’s Advisory Committee on Immunization Practices (ACIP) will add HEPLISAV-B to its adult vaccination schedule during its February 2018 meeting, or at all; whether potential claims against us, including those based on patent rights of others, will result in an injunction against sales or otherwise impact commercialization and sales; and the results of clinical studies of Dynavax’s product candidates, such as SD-101, and the impact of those results on the initiation or continuation of subsequent studies for those product candidates, and issues arising in the regulatory process; and other risks detailed in the “Risk Factors” section of our most recent current periodic report filed with the SEC. These statements represent our estimates and assumptions only as of the date of this press release. We do not undertake any obligation to update publicly any such forward-looking statements, even if new information becomes available. Information on Dynavax’s website at www.dynavax.com is not incorporated by reference in our current periodic reports with the SEC.

(i) CDC. https://www.cdc.gov/hepatitis/statistics/2015surveillance/index.htm#tabs-5-8. Fig 3.2

(ii) Nelson J, et al. Compliance with multiple-dose vaccine schedules among older children, adolescents and adults: results from a Vaccine Safety Datalink Study. American Journal of Public Health. 2009;99:S2.

(iii) CDC. https://www.cdc.gov/hepatitis/hbv/bfaq.htm.

(iv) CDC. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm.

(v) CDC. https://www.cdc.gov/diabetes/pubs/pdf/hepb_vaccination.pdf.

(vi) CDC. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf.

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Highlights from the CHMP November meeting http://www.eatg.org/news/highlights-from-the-chmp-november-meeting/ Sat, 11 Nov 2017 21:56:49 +0000 http://www.eatg.org/?post_type=news&p=6751 At its November meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended for approval two generic versions of darunavir – Darunavir Krka and Darunavir Krka d.d. for the treatment of HIV infection.

Summary of opinion for Darunavir Krka is available here.
Summary of opinion for Darunavir Krka d.d. is available here.

CHMP also recommended an extension of therapeutic indications for Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) with marketing authorisation holder Gilead Sciences International Limited.

Summary of opinion for Genvoya is available here.

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Understanding the Berlin patient’s unexpected cure of HIV http://www.eatg.org/news/understanding-the-berlin-patients-unexpected-cure-of-hiv/ Sat, 11 Nov 2017 21:54:30 +0000 http://www.eatg.org/?post_type=news&p=6757 New tool developed to study stem cell transplants as a potential way to treat HIV

A decade ago, the medical world was shocked when a patient in Berlin, Germany, had been declared free of HIV after receiving a stem cell transplant to treat cancer. Doctors have repeatedly tried to replicate the result, but this HIV cure has evaded other patients so far.

Dr. Jonah Sacha and colleagues at OHSU’s Vaccine & Gene Therapy Institute are among the many scientists who are seeking to understand why the much-studied “Berlin patient” was so fortunate. Now, they’ve developed a new way to understand his cure. Sacha’s team has shown a species of monkey called Mauritian cynomolgus macaques can successfully receive stem cell transplants.

Researchers have long used a different monkey species to research stem cell transplants, but that species’ biological characteristics means it can’t be reliably used to find good donor matches to mimic human stem transplants.

In a paper published Nov. 10 in the journal Nature Communications, Sacha and colleagues report they successfully performed stem transplants on two monkeys more than a year ago that continue to lead healthy lives today. The recipients did not suffer from the many common adverse effects of stem transplants, including the grueling graft-versus-host disease, which can cause severe liver damage, rashes, diarrhea and even death.

The finding provides Sacha a critical tool needed to explore how the Berlin patient was cured. As a result of the finding, researchers can also use Mauritian cynomolgus macaques to improve stem cell transplant outcomes for human patients with other blood-related conditions such as leukemia and sickle-cell disease.

Journal Reference:

  1. Benjamin J. Burwitz, Helen L. Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W. Legasse, Katherine B. Hammond, Stephanie L. Junell, Jason S. Reed, Benjamin N. Bimber, Justin M. Greene, Gabriela M. Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K. Axthelm, Rebecca Ducore, Anne Lewis, Lois M. A. Colgin, Theodore Hobbs, Lauren D. Martin, Betsy Ferguson, Charles R. Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J. Stanton, Richard T. Maziarz, Jonah B. Sacha. Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-01631-z
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Traditional interventions can prevent cardiovascular disease in patients with HIV http://www.eatg.org/news/traditional-interventions-can-prevent-cardiovascular-disease-in-patients-with-hiv/ Sat, 11 Nov 2017 21:52:16 +0000 http://www.eatg.org/?post_type=news&p=6759 Traditional methods for preventing cardiovascular disease can maximize the cardiovascular health of patients with HIV and defray future health care costs, according to findings published in Clinical Infectious Diseases.

“Although cardiovascular pathophysiology in the HIV context is not yet fully understood, likely mechanisms include complex interactions between traditional and HIV-related risk factors,” Mikaela Smit, PhD, research associate in the department of infectious disease epidemiology, Imperial College London, and colleagues wrote. “Prevention interventions will need to be firmly integrated into HIV care and supported by evidence-based studies in order to effectively mitigate the emerging [cardiovascular disease] burden, mortality risk and impact on quality of life of [people living with HIV].”

The researchers created an individual-based model of cardiovascular disease in 8,791 patients with HIV who were receiving ART, all of whom were included in the Dutch national AIDS Therapy Evaluation in the Netherlands, or ATHENA, cohort. The model followed patients as they aged and developed and then began treatment forcardiovascular disease. Smit and colleagues evaluated four different prevention interventions: earlier diagnosis and treatment of HIV, avoiding combination ART in the presence of increased cardiovascular risk, smoking cessation and more intensive monitoring and treatment of dyslipidemia and hypertension.

Most patients (77.9%) were male, and slightly more than half (52.5%) were MSM. Median age was 43.8 years. The model predicted a 55% increase of cardiovascular disease among patients with HIV between 2015 and 2030, Smith and colleagues reported, while costs were predicted to rise by 36%. Smoking cessation averted 13.1% of cases of cardiovascular disease in the model, whereas intensified monitoring and treatment of hypertension averted 20%. These traditional methods were significantly more effective than earlier HIV diagnosis and treatment, which averted a projected 0.8% of cases, and avoiding combination ART with increased cardiovascular risk, which avoided 3.7% of cases, the researchers wrote.

Smit and colleagues added that targeting high-risk patients “could avert the majority of events and costs.

“Intensified monitoring and successful treatment of hypertension and dyslipidemia in [people living with HIV] is expected to be the most feasible intervention accompanied by the largest cardiovascular health benefit and could safeguard quality of life of HIV-positive people,” the researchers wrote.

Smit M, et al. Clin Infect Dis. 2017;doi:10.1093/cid/cix858.

By Andy Polhamus

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CVD, CKD should be assessed together in HIV-positive patients http://www.eatg.org/news/cvd-ckd-should-be-assessed-together-in-hiv-positive-patients/ Sat, 11 Nov 2017 21:50:18 +0000 http://www.eatg.org/?post_type=news&p=6760 HIV-positive patients at predicted risk for cardiovascular disease (CVD) and chronic kidney disease (CKD) are at an even greater risk for CVD and CKD events, according to new research published in PLOS Medicine.

First author Mark A. Boyd, MD, and a team confirmed their hypothesis that predicted risk scores would translate to a higher risk of disease after evaluating a large-scale cohort of 27,215 HIV-positive individuals. Boyd and colleagues drew their pool of participants from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, which has its own specialized predictive risk models for CVD and CKD in the HIV-positive population.

Nearly 50,000 patients are enrolled in the D:A:D study, which stretches across countries worldwide and aims to establish whether the use of combination antiretroviral therapy is associated with increased risks of conditions like CVD, end-stage renal disease, liver disease, cancer and death. These combination antiretroviral therapies have “transformed the lives of HIV-positive people” in high-income countries, Boyd et al. wrote, but though the drugs have been linked to decreased disease rates and increased life expectancy, evidence also exists that the medication can lead to greater and earlier onset comorbidities.

CVD and CKD are diseases that feed one another, the authors explained—CKD is an established independent risk factor for CVD and the two conditions share a handful of risk factors.

“It is well recognized that the effects of comorbidity may be greater than the effects of the sum of risk of each disease, and that their coexistence may lead to more severe illness, poorer prognosis and premature death,” they wrote.

For their study, the researchers pulled D:A:D participants who had recorded predicted risk scores for CVD and CKD higher than the general HIV-positive population. The risk equations predicted 13.1 percent of those patients at high CVD risk, 18.4 percent at high CKD risk and 5.8 percent at high risk for both diseases. CVD and CKD event rates were calculated by predicted five-year CVD and CKD risk groups and were multiplicative, Boyd and colleagues reported. The strongest finding was that CVD and CKD are especially dangerous when they come hand-in-hand.

The authors said these findings suggest a possible need to monitor HIV-positive patients more closely when it comes to CVD and CKD risk factors.

“We found that people at high predicted risk for both CVD and CKD have substantially greater risks for both CVD and CKD events compared with those at low predicted risk for both outcomes, and compared to those at high predicted risk for only CVD or CKD events,” Boyd et al. wrote. “This suggests that CVD and CKD risk in HIV-positive persons should be assessed together.”

By Anicka Slachta

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Ireland’s first clinic monitoring anti-HIV drug PrEP opens http://www.eatg.org/news/irelands-first-clinic-monitoring-anti-hiv-drug-prep-opens/ Sat, 11 Nov 2017 21:29:05 +0000 http://www.eatg.org/?post_type=news&p=6748 Clinic will be open to users of PrEP and will provide HIV tests and STI screening

9 November 2017: Ireland’s first clinic for monitoring users of anti-HIV drug PrEP will open in Dublin on Thursday.

Pre-Exposure Prophylaxis (PrEP) is a once-daily medication that has been proven to reduce the risk of HIV infection, particularly among members of the gay community, by up to 90 per cent.

The clinic will be open to users of the drug and will provide HIV tests and STI screening; it will not supply the drug.

The clinic will be open on Baggott street in Dublin every Thursday from 10-12am.

PrEP may not be available under the HSE payment scheme until 2019, a delay that could see up to 800 new infections, health groups have warned.

The cost of PrEP is not covered by the HSE, although it can be obtained privately with a doctor’s prescription at a cost of € 400 a month.

Gay rights activists say most people can’t afford this, leading many to import it from abroad, a practice which is illegal in Ireland.

The HSE said an assessment was taking place on whether it would be cost effective for it to cover the cost of the drug.

The assessment is being carried out by the National Centre for Pharmacoeconomics (NCPE).

In June the NCPE conducted a “rapid review” which is an initial assessment of the drug.

This was completed in late July and a full assessment was recommended.

However, this assessment cannot progress until the manufacturers of the PrEP, Gilead Sciences, make a formal application to the HSE.

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Danish court invalidates Gilead SPC http://www.eatg.org/news/danish-court-invalidates-gilead-spc/ Sat, 11 Nov 2017 21:23:29 +0000 http://www.eatg.org/?post_type=news&p=6747 The Danish Maritime and Commercial High Court has invalidated a supplementary protection certificate (SPC) owned by Gilead.

On October 26, the court rejected Gilead’s motion for an injunction against generics maker Accord.

Gilead’s SPC, number CR 2005 00032, covers the combination of emtricitabine and tenofovir disoproxil.

It was issued for Danish patent EP 0,915,894, called “Nucleotide analogs”, which expired in July this year.

Gilead sells emtricitabine/tenofovir under the brand name Truvada, to treat and prevent HIV/AIDS.

According to the court, Gilead was informed in May 2017 that Accord had obtained a marketing authorisation (MA) for the drug “emtricitabine/tenofovir disoproxil Accord”.

Gilead then contacted Accord, asking the generics maker not to market these products until the SPC was no longer in force.

In June, Gilead sent a follow-up letter to Accord, as Accord had not responded.

This time, Accord responded, claiming that its product didn’t infringe because the tenofovir disoproxil contained in its drug was not present in its fumarate acid state (which was protected under the certificate), and that the SPC was invalid.

Gilead claimed that the SPC covers tenofovir disoproxil in its various forms, in combination with other therapeutic components such as emtricitabine.

The court backed Gilead, finding that company had made it probable that the SPC covered the active ingredients listed in the MA, namely emtricitabine and tenofovir disoproxil, in all pharmaceutical forms.

Turning to the validity of the SPC, the court discussed claim 27 of the patent, on which the SPC was based.

The claim covers a compound (as described in claims 1-25), together with a pharmaceutically acceptable carrier and, optionally, other therapeutic ingredients.

According to Gilead, the SPC had been issued in accordance with article 3(a) of the SPC regulation, and the combination was protected.

The Danish court, citing the Court of Justice of the European Union (CJEU) in Medeva (case C-322/10), noted that article 3(a) must be interpreted as precluding the issuance of an SPC which contains active ingredients that do not appear in the wording of the requirements of the basic patent relied on.

Eli Lilly (C-493/12), a judgment by the CJEU in 2013, was also quoted as stating that an active ingredient not mentioned in the basic patent requirement is not protected under article 3(a).

The court also mentioned guidelines from the Danish Patent and Trademark Office on SPCs, which note that “a combination product consisting of the two active ingredients A and B is considered to be protected by a basic patent when combinations A and B appear from the wording of the requirements”.

According to the court, emtricitabine is not apparent from the wording of claim 27, so Accord had established that the contested SPC was invalid.

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Healthcare workers living with HIV have different motivations for disclosing or concealing their HIV status http://www.eatg.org/news/healthcare-workers-living-with-hiv-have-different-motivations-for-disclosing-or-concealing-their-hiv-status/ Sat, 11 Nov 2017 21:16:44 +0000 http://www.eatg.org/?post_type=news&p=6746

Nurses and other healthcare workers who are living with HIV have mixed reactions when they mention their HIV status to colleagues, according to a small Dutch study reported in the November/December issue of the Journal of the Association of Nurses in AIDS Care. Some healthcare workers disclosed because they expected a positive reaction or they felt the need to share a secret. Others concealed their HIV status because they feared a negative reaction or did not believe that disclosure was relevant or necessary.

Many people with HIV discuss their HIV status with partners, friends and family, but conceal it with employers and colleagues. Moreover, there can be particular difficulties for people working in healthcare, because of anxieties about infection control. Nonetheless, Sarah Stutterheim found that all previous studies investigating the experiences of healthcare providers with HIV were conducted in sub-Saharan Africa, with none from a European context.

She recruited ten healthcare workers living with HIV by placing an advertisement on the Dutch HIV Association’s website and through snowball sampling. The participants took part in face-to-face interviews in 2011 and 2012.

Six were nurses, three were nursing assistants and one was a pharmacist. Workplace settings were varied – general hospitals, a psychiatric hospital, nursing homes for the elderly, a group home for people with disabilities and a pharmacy.

Nine participants were gay men and one was a heterosexual woman. All were Dutch. Their mean age was 46 and they had been diagnosed for a mean of nine years.

Disclosing or concealing

Three participants reported making a conscious choice to be open about their HIV at work. Two others said they did not explicitly hide their HIV status, but were not particularly open about it either. As one of them said:

‘‘I would never deny it if people were to ask but I wouldn’t go up to my new colleagues and say, ‘I have to tell you something: I have HIV.’’’

Two interviewees had made a conscious decision to conceal their HIV status. A further three had previously been open at work, but were not anymore.

The motivations of those who chose to disclose at work varied. Some felt that it would be cathartic.

‘‘It felt like the more open I was about it, the more I felt set free, and I became happier by, by just sharing it.’’

Others expected the reaction to be positive.

‘‘I don’t feel like hiding it at work… We have lots of clients with HIV so it’s pretty normal.’’

‘‘There was another guy in my department who was also HIV positive and he was open about it so I knew that it was a safe environment for me to talk about it.’’

Others felt that by being proactive, they could prevent future problems:

‘‘So that all my colleagues would hear it from me, to prevent it from spreading through the hospital as gossip.’’

In contrast, half the participants were concealing their HIV status at work at the time of the interview. A key motivation for this was that they expected negative reactions or stigma, often because they had previously experienced this themselves or had seen it occur in relation to other people.

“I’m not going to tell them anymore because I’m, yeah, I’m scared of how my colleagues will react. And where does this come from? It comes from, for example, the fact that whenever a patient is admitted and he has HIV, then they immediately say, ‘You need to be careful, eh? He has HIV so be extra careful’.”

One nurse said that he no longer discussed his status because of a “horribly disastrous” experience with a former employer.

“I was basically removed from my position there. I was allowed to stay in the department but I wasn’t allowed to do any patient treatment or activities anymore, so basically it became an administrative job.”

A very different reason not to disclose HIV status relates to the normalisation of HIV – participants did not see the relevance or necessity of discussing HIV with colleagues.

“Who am I accountable to? Accountability: what a word, eh? I mean do I really have to automatically tell them everything about me? If I have something, do I immediately have to tell my colleagues, I have this or that? No, I don’t.”

“I haven’t told anyone there. I’ve gotten to the point where, it’s part and parcel and, I don’t need – I don’t feel the need to talk about, to tell people. I no longer have that need to talk about it with everyone.”

Those who hid their status said that concealment could sometimes be difficult. They reported fears of being discovered, for example when colleagues saw them taking medication or if they had periods of sickness.

“You only realize after the fact just how much energy it costs to live with a secret and that’s especially the case when things start to shift and they get complicated because there comes a point when you can’t remember who you’ve told and who you haven’t told.”

Reactions to disclosure

Many participants had had positive reactions to disclosure. Some colleagues and managers responded with interest, support and empathy. Very often, those disclosed to saw the participant’s HIV status as a non-issue.

“Basically, it was like there was a peak but that peak came and went really fast. So, what it comes down to is that, in the beginning, it was talked about and thought about a lot but that was, at a given moment, gone and nobody gave it anymore thought.”

Other interviewees noted with satisfaction that their confidentiality had been maintained.

A few participants had experienced negative reactions, including management wanting to reassign duties or inform colleagues about the person’s status.

“She [team leader] wanted to inform human resources and the management about my HIV status because I was a risk to the department for both patients and my colleagues. And I tried to explain that HIV can’t be transmitted in normal social contact, but she wasn’t so sure of that. And I told her that she couldn’t do that, that she couldn’t simply decide to tell others that I’m HIV-positive because it violates privacy laws. And she just got really angry. She said to me, ‘Well, I believe, in this situation, you are in no position to make demands’.”

Some said they were gossiped about or found it difficult to find new work. Experiences like these had a substantial negative impact.

“It hit me like a bomb. I was totally floored… I was very emotional and I couldn’t put it in perspective.”

“I felt down. I felt really small.”

Some confronted colleagues with accurate information (for example about infection risks), some distanced themselves by attributing the reaction to ignorance, others sought support from colleagues – and two of the ten respondents decided to find work elsewhere.

Recommendations

Sarah Stutterheim and colleagues suggest the development of specialised counselling services for employees with HIV which could help with disclosure decisions. Such services should emphasise that disclosure is a choice. They should help employees to explore their motivations for disclosure (or concealment) and the potential reactions if they do disclose. The authors comment that while disclosure can be beneficial if it results in social support or reduces psychological stress, it may sometimes be more advantageous to conceal at work, especially when the risks are great and social support is available elsewhere.

This kind of counselling should include role-play, to help people prepare for disclosure and dealing with negative reactions. It should also focus on developing coping skills and building resilience.

Meanwhile, health care organisations should make workplaces safe for people living with HIV through inclusive workplace policies and structures, initiatives that increase HIV knowledge, and efforts to enhance contact between people living with HIV and others.

By Roger Pebody

Reference

Stutterheim SE et al. HIV status disclosure in the workplace: Positive and stigmatizing experiences of health care workers living with HIV. Journal of the Association of Nurses in AIDS Care 28: 923-937, 2017.

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Fighting TB stigma: we need to apply lessons learnt from HIV activism http://www.eatg.org/news/fighting-tb-stigma-we-need-to-apply-lessons-learnt-from-hiv-activism/ Sat, 11 Nov 2017 21:10:58 +0000 http://www.eatg.org/?post_type=news&p=6745 BMJ Global Health published an article on TB stigma and how lessons learnt from HIV activism can be successfully applied to confront the TB-related stigma.

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TAG releases new report on TB research funding http://www.eatg.org/news/tag-releases-new-report-on-tb-research-funding/ Thu, 09 Nov 2017 20:27:37 +0000 http://www.eatg.org/?post_type=news&p=6738 Higher funding for TB research signals hope, but governments must dramatically increase spending to end TB.

Before the World Health Organization Global Ministerial Conference on Ending TB in the Sustainable Development Era, advocates call on all countries to increase support for TB research to reach global targets.

NEW YORK, NOVEMBER 8, 2017—Global funding for tuberculosis (TB) research reached a previously unreported high of $726 million in 2016, according to a report released today by Treatment Action Group (TAG) and the United Nations–hosted Stop TB Partnership. This represents a $100 million increase over 2015 levels and marks the first time annual funding for TB research and development (R&D) has exceeded $700 million since TAG began tracking spending in 2005. Although higher than in previous years, this amount remains woefully inadequate when judged against the innovation gaps holding back the response to TB, which is the world’s leading cause of death from a single infectious agent.

In October, the World Health Organization (WHO) announced that TB killed 1.7 million people in 2016 and caused 10.4 million new cases of TB disease. “WHO’s new TB burden estimates highlight the persistent lethality of the TB epidemic in the face of chronic underfunding and limited scientific progress,” said Mark Harrington, TAG executive director. “Exceeding $700 million in funding for TB R&D in 2016 is a hopeful sign, but with at least $2 billion needed annually, this must be the preliminary ascent, not the peak. We have to make up for decades of underinvestment and scientific neglect.” The Stop TB Partnership estimates that the world needs to spend $9 billion on TB R&D from 2016 to 2020 to stay on track with the global goal of ending TB by 2030.

TAG released the report, The Ascent Begins: Tuberculosis Research Funding Trends, 2005–2016, a week before ministers of health and high-ranking officials from over 90 countries will meet in Moscow at the first Global Ministerial Conference on Ending TB in the Sustainable Development Era, convened by the WHO and hosted by the government of the Russian Federation. The Ministerial Conference will culminate in a signed political declaration committing ministers of health and other agencies to work with each other and within their governments to end the TB epidemic by 2030, as called for by the United Nations Sustainable Development Goals (SDGs) and the WHO End TB Strategy. That strategy indicates that universal access to currently existing technologies will not be enough to reduce TB incidence and mortality to the desired near-elimination levels; instead, ending TB by 2030 will require introducing new tools to prevent, diagnose, and treat TB no later than 2025.

“Ministerial engagement on TB R&D is important, but unless we have heads of state committing to fill the TB research funding gap, we will go nowhere,” said Dr. Lucica Ditiu, executive director of the Stop TB Partnership. “We must raise the TB R&D topic on the political agenda, through our continuous advocacy, and the first-ever United Nations High-Level Meeting on Tuberculosis in 2018. And political commitments and discussions must translate into concrete actions. Governments must increase their spending on TB research to develop the innovations we need to end TB.”

The TAG/Stop TB Partnership report cautions that the spending increase observed in 2016 is mostly attributable to existing major donors such as the U.S. National Institutes of Health and the Bill & Melinda Gates Foundation, which together have contributed over half of all reported funding for TB research since 2005. Pharmaceutical industry expenditures on TB R&D declined for the fifth straight year.

###

Download the report The Ascent Begins: Tuberculosis Research Funding Trends, 2005–2016

More information:

  1. Country-Specific TB Research Funding Targets
  2. WHO Global Ministerial Conference on Ending Tuberculosis
  3. G20 Leaders Declaration (para. 22 mentions TB R&D)
  4. BRICS Leaders Xiamen Declaration (para. 64 mentions TB R&D)

About TAG

Treatment Action Group is an independent, activist, and community-based research and policy think tank fighting for better treatment and prevention, a vaccine, and a cure for HIV, TB, and hepatitis C virus (HCV). TAG works to ensure that all people with HIV, TB, and HCV receive lifesaving treatment, care, and information. We are science-based treatment activists working to expand and accelerate vital research and effective community engagement with research and policy institutions.

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WHO compendium of TB guidelines and associated standards http://www.eatg.org/news/compendium-of-who-guidelines-and-associated-standards/ Thu, 09 Nov 2017 20:25:58 +0000 http://www.eatg.org/?post_type=news&p=6736 Compendium of WHO guidelines and associated standards: ensuring optimum delivery of the cascade of care for patients with tuberculosis

3 November 2017 | Geneva: The Global Tuberculosis Programme of the World Health Organization (WHO) has released the “Compendium of WHO guidelines and associated standards” to support the delivery of care for all persons affected by tuberculosis (TB).

The Compendium has been developed as a clear and concise instrument to facilitate the understanding and planning of delivery of high-quality care for everybody affected by TB. It incorporates all recent policy guidance from WHO; follows the care pathway of persons with signs or symptoms of TB in seeking diagnosis, treatment and care; and includes key algorithms and cross-cutting elements that are essential to a patient-centered approach in the cascade of TB care.

The Compendium is structured into 33 WHO standards and consolidates all current WHO TB policy recommendations into a single resource, with electronic links to the individual, comprehensive WHO policy guidelines.

Background

Ending the TB epidemic requires speedy adoption and implementation of the WHO End TB Strategy [1] to reach its the ambitious targets, within the framework of the United Nations Sustainable Development Goals. This in turn requires implementation and scale-up of the most modern standards for TB  prevention, diagnosis and treatment, supported by cross-cutting elements such as ethics and human rights and with significantly enhanced human and financial resources.

Beyond accelerated implementation of existing tools, an effective TB response must embrace innovation through the rapid uptake of new interventions such as diagnostics, medicines, and digital platforms to modernize care provision. Working with communities, civil society and any partners, governments need to assume full responsibility for ensuring access to person-centered, modern, high-quality TB services, regardless of whether care is sought from public, voluntary, private or corporate care providers. Securing comprehensive care along with essential support for each person with TB also calls for collaboration within and beyond the health sector.

“After decades of stagnation, finally new diagnostics, drugs and regimens have become available through intensified research efforts and increased field experiences,” said Dr Mario Raviglione, Director of the WHO Global TB Programme. “Implementing the standards of TB care outlined in this Compendium will ensure that these innovations rapidly translate into optimal care for all affected by TB.”

The Compendium will be updated annually, including in its digital format, to allow incorporation of new evidence emerging from the rapidly evolving TB diagnostic and treatment landscape.

[1] Implementing the End TB Strategy: the essentials (WHO/HTM/TB/2015.31). Geneva, World Health Organization. 2015. (http://www.who.int/tb/publications/2015/end_tb_essential.pdf; accessed 2 November 2017).

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FDA guidance for industry on DAA development for hepatitis C http://www.eatg.org/news/fda-guidance-for-industry-on-daa-development-for-hepatitis-c/ Thu, 09 Nov 2017 20:20:12 +0000 http://www.eatg.org/?post_type=news&p=6742 FDA published a final guidance on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. The guidance can be found at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm225333.pdf

This guidance assists sponsors in the clinical development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) from the pre-investigational new drug application stage through the new drug application and post-marketing stages.  This guidance finalizes the draft guidance of the same name issued in May 2016.  Major changes from the draft include the following:

  • Modification of several sections to focus on interferon-free DAA regimens.
  • Additional clarification on trial designs for combinations of investigational DAAs with or without ribavirin.
  • Additional clarification on the recommended trial population to include patients with clinical or laboratory evidence of CHC disease.
  • Additional details on DAA drug development in patients with decompensated cirrhosis.
  • Additional clarification on efficacy endpoints.
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Fact sheets on global health R&D http://www.eatg.org/news/fact-sheets-on-global-health-rd/ Thu, 09 Nov 2017 20:15:30 +0000 http://www.eatg.org/?post_type=news&p=6735 The Global Health Technologies Coalition (GHTC) released a six-part fact sheet series examining the contributions of the US government agencies to advancing global health R&D, including USAID, NIH, CDC, FDA, DoD, and BARDA.

The fact sheets can be downloaded here.

 

The Kaiser Family Foundation released an updated fact sheet explaining the US government’s role in addressing global TB, including the history of the US involvement and funding trends.

The fact sheet can be downloaded here.

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Gilead loss of generic HIV drug battle a boost for gay community in Ireland http://www.eatg.org/news/gilead-loss-of-generic-hiv-drug-battle-a-boost-for-gay-community-in-ireland/ Thu, 09 Nov 2017 20:09:42 +0000 http://www.eatg.org/?post_type=news&p=6741 Generic versions of Truvada that are 60 per cent cheaper are about to hit Irish market

A campaign by Ireland’s gay and transgender community for access to cheaper drugs to treat and prevent HIV has received a major boost, after pharma giant Gilead lost a court action in Dublin against generics manufacturers.

Gilead has generated almost $14 billion globally in recent years from sales of its blockbuster HIV drug, Truvada. It came off patent in July, but its Irish exclusivity is extended until 2020 by a supplementary protection certificate (SPC).

In July, Gilead initiated High Court action against generics manufacturers Mylan and Teva, who planned to launch generic versions in Ireland upon patent expiry. Gilead sought an injunction blocking them due to the SCP.

This week, however, the court rejected its application for an interlocutory [provisional] injunction, which would have blocked Mylan and Teva until a full trial.

Sources say that the launch of generic versions of Truvada by Mylan and Teva in Ireland is now imminent. They will be up to 60 per cent cheaper.

Access to Truvada and its generic equivalents is at the heart of a passionate campaign in Ireland and abroad. Primarily for men who have sex with other men, the drug has three uses: to treat HIV once contracted; as part of a preventative cocktail taken immediately after possible exposure; and, taken routinely to help reduce the risk of contracting HIV.

The Health Service Executive (HSE) spends about €24 million on Truvada as a treatment and also for immediate post-exposure prophylaxis (PEP) treatment. The State does not, however, fund Truvada for pre-exposure (PrEP) use, which is at the heart of the campaign by advocates for the gay community.

Some studies have shown that taking a PrEP drug as a preventative measure reduces contraction rates among men who have sex with men by 90 per cent.

In its High Court action, Gilead sought the injunction and also for Mylan and Teva to “deliver up” their plans for their products. Mylan responded that it already has “pricing approval” from the State for its generic version, while Teva also said it would not wait on the expiration of the SPC.

SPCs for Truvada are being challenged in several countries across Europe by Mylan and Teva, including the UK, Spain and Germany. They have not sought to revoke the SPC in Ireland. Meanwhile, Gilead failed to get an interim injunction in France, but its SPC was upheld in Portugal.

Mr Justice Brian McGovern rejected Gilead’s injunction application, partly on the basis that if it is found at full trial that the SPC stood and its rights were breached, Gilead could seek monetary damages.

Andrew Leavitt, a member of campaign group Act Up Dublin, welcomed this week’s “significant” decision, which he said could “accelerate the timeline” for State-funded PrEP because the generics are 60 per cent cheaper.

He said many gay men order the drug online themselves at a cost of €100 for a three-month preventative supply, but customs often seize it on importation in the post.

“We don’t care who the HSE acquires PrEP from, we just want it available in Ireland,” said Mr Leavitt.

Gilead did not make any comment about the judgment.

By Mark Paul

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Scientists find missing clue to how HIV hacks cells to propagate itself http://www.eatg.org/news/scientists-find-missing-clue-to-how-hiv-hacks-cells-to-propagate-itself/ Thu, 09 Nov 2017 19:58:57 +0000 http://www.eatg.org/?post_type=news&p=6740

Computer modeling has helped a team of scientists, including several scholars from the University of Chicago, to decode previously unknown details about the process by which HIV forces cells to spread the virus to other cells. The findings, published Nov. 7 in Proceedings of the National Academy of Sciences, may offer a new avenue for drugs to combat the virus.

A key part of HIV’s success is a nasty little trick to propagate itself inside the body. Once HIV has infected a cell, it forces the cell to make a little capsule out of its own membrane, filled with the virus. The capsule pinches off—a process called “budding”—and floats away to infect more cells. Once inside another unsuspecting cell, the capsule coating falls apart, and the HIV RNA gets to work.

Scientists knew that budding involves an HIV protein complex called Gag protein, but the details of the molecular process were murky. “For a while now we have had an idea of what the final assembled structure looks like, but all the details in between remained largely unknown,” said Gregory Voth, the Haig P. Papazian Distinguished Service Professor of Chemistry and corresponding author on the paper.

Since it’s been difficult to get a good molecular-level snapshot of the protein complex with imaging techniques, Voth and his team built a computer model to simulate Gag in action. Simulations allowed them to tweak the model until they arrived at the most likely configurations for the molecular process, which was then validated by experiments in the laboratory of Jennifer Lippincott-Schwartz at the National Institutes of Health and the Howard Hughes Medical Institute Janelia Research Campus.

They built a model of missing parts of the Gag protein complex, and tweaked it until they could see how the proteins assemble by taking advantage of cellular infrastructure in preparation for the budding process.

“It really demonstrates the power of modern computing for simulating viruses,” Voth said.

“The hope is that once you have an Achilles’ heel, you can make a drug to stop Gag accumulation and hopefully arrest the virus’s progression.”

The team plans next to study the structures of the Gag proteins in the HIV virus capsule after budding, he said.

Other UChicago authors on the paper were postdoctoral researcher Alexander Pak, researcher John Grime and graduate student Aleksander Durumeric.


Citation: “Immature HIV-1 Lattice Assembly Dynamics are Regulated by Scaffolding from Nucleic Acid and the Plasma Membrane,” Pak et. al., Proceedings of the National Academy of Sciences, Nov. 7, 2017. doi: 10.1073/pnas.1706600114

Funding: National Institutes of Health, Howard Hughes Medical Institute, European Molecular Biology Laboratory, Chica un Heinz Schaller Siftung, Deutsche Forschungsgemeinschaft, National Science Foundation, State of Illinois.

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Undetectable = Untransmittable: a community brief http://www.eatg.org/news/undetectable-untransmittable-a-community-brief/ Wed, 08 Nov 2017 22:44:58 +0000 http://www.eatg.org/?post_type=news&p=6726 The International Council of AIDS Service Organizations (ICASO) developed a brief to provide the HIV community with current information and analysis of new and updated clinical data on the effectiveness of antiretroviral therapy (ART) in preventing HIV transmission to sexual partners of people living with HIV. While the health benefits of treatment will always be the primary purpose of ART, it is vital that the secondary benefits to people living with HIV and their sexual partners be fully understood and communicated. The brief is organized as follows:

  1. Introduction
  • Overview of the rationale for this brief as well as a glossary of key terms
  1. HIV Basics: Prevention, Sexual Transmission and the Dual Role of Anti-retrovirals
  • Overview of current global information on sexual transmission, combination HIV prevention packages and the dual role of ART in improving the health of people living with HIV and preventing sexual transmission to sexual partners
  1. The Science of HIV Transmission: What’s New?
  • Summary of clinical findings released in 2016 and early 2017 on the role of ART in preventing transmission to sexual partners of people living with HIV
  • Brief review of the clinical evidence regarding the use of ARVs as oral pre-exposure prophylaxis (PrEP) by HIV-negative people to prevent HIV acquisition
  1. Advocacy for Access to ART and HIV diagnostics
  • Analysis of implications of new and updated clinical findings in developing advocacy strategies to address disparities in access to HIV diagnostics including viral load testing and ART.
  1. Advocacy for Accurate, Rights-based HIV Education: Challenging HIV Stigma
  • Analysis of implications of new and updated clinical findings in developing rights-based HIV education for people living with HIV
  1. The Population Potential of ARVs as Prevention
  • Analysis of the population potential of ARVs in reducing or eliminating sexual transmission of HIV
  1. Law Reform on Criminalization of HIV Non-Disclosure
  • Implications for advocacy for law reform efforts aimed at ending the unjust, overly-broad application of general and HIV-specific laws which criminalize people living with HIV
  • ICASO’s position is consistent with international guidance on restricting the use of criminal law to exceptional circumstances of intentional, actual transmission.

 

Download the community brief here.

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Advances in HIV prevention, treatment and cure: a special issue of PLOS Medicine http://www.eatg.org/news/advances-in-hiv-prevention-treatment-and-cure-a-special-issue-of-plos-medicine/ Wed, 08 Nov 2017 22:41:59 +0000 http://www.eatg.org/?post_type=news&p=6733 Senior Editor Richard Turner discusses the content published in week 1 of the PLOS Medicine Special Issue on HIV/AIDS.

This week, PLOS Medicine begins publication of a Special Issue on Advances in HIV Prevention, Treatment and Cure, advised by Guest Editors Linda-Gail Bekker, Steven Deeks and Sharon Lewin of the Desmond Tutu HIV Centre, University of Cape Town, South Africa; the University of California, San Francisco, USA; and the Peter Doherty Institute of Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Australia, respectively. The issue will feature research and discussion content addressing one of the world’s most critical health challenges.

Developing scientific and societal solutions to control the spread of the HIV epidemic has been a long struggle, drawing on commitment and advocacy from many quarters, including researchers, donors, activists and patients, including many in low- and middle-income countries. Today, potent methods for prevention and treatment of HIV infection are widely available, but the wide geographic spread of the virus and its prevalence within vulnerable population groups mean that the scale of the epidemic remains a serious problem—in 2016, there were an estimated 1.8 million new HIV infections and 1 million deaths from AIDS-related illnesses, a large proportion in low- and middle-income countries.

In a Research Article in PLOS Medicine, Tonia Poteat and colleagues address the situation of a key population at risk of HIV/AIDS—transgender women and men who have sex with men (MSM) in Africa. In an analysis of survey data on more than 4,500 participants from 8 countries, Poteat and colleagues document a greater risk of HIV infection for transgender women as compared with other MSM, and report on behavioural risk factors associated with HIV infection and on participants’ experiences of stigma and violence. Such findings should be valuable in guiding the design of programmes to engage with, and address the challenges around provision of prevention and care for, this at-risk group.

With the goal of ending the HIV epidemic in mind, the Joint United Nations Programme on HIV/AIDS (UNAIDS) has set demanding targets for achieving high coverage of HIV testing, as well as effective and sustained treatment of people who are infected, across all countries. As an example of the issues of engaging and retaining patients in care, Samantha Kaplan and colleagues report in their Research Article on a longstanding programme for provision of HIV therapy in Khayelitsha township in South Africa. The authors estimate that around 25% of patients disengaged from care over 2 years, although a proportion of these patients were found to have subsequently re-engaged in care. These findings indicate the difficulties of providing effective therapy for a mobile population in such settings.

In a further Research Article, Margaret McNairy and colleagues report the findings of Link4Health, a cluster-randomized trial carried out in Swaziland. With an aim of improving the engagement of and retention in care of people with HIV, the authors tested a combination intervention including prompt HIV testing and initiation of antiretroviral therapy, together with other approaches to support provision of care. Substantial benefits in engagement and retention in care up to 1 year are reported, indicating the promise of combined approaches to increase population coverage with effective treatment. In a Perspective entitled “Reaching global HIV/AIDS goals: What got us here, won’t get us there”, Wafaa El-Sadr and coauthors discuss the importance of tailoring HIV therapy and care to specific settings and population groups.

The ultimate solution to the HIV/AIDS epidemic would be to develop a reliable method to cure HIV infection, but to date this has been achieved very rarely. Timothy Henrich and colleagues address this topic in a Research Article, in which they describe detailed studies carried out on two people participating in pre-exposure prophylaxis programmes. These individuals started antiretroviral treatment a few days after HIV infection, and one patient subsequently underwent an analytical treatment interruption; Henrich and colleagues studied the characteristics and distribution of the viral reservoir for more than two years. Although cure was not achieved in either of these patients, such analyses should be able to inform future strategies intended to eradicate HIV from people with the infection.

Effective antiretroviral therapy means that people are now living with HIV for many years, and large population studies such as D:A:D (Data collection on Adverse events of Anti-HIV Drugs) are important to monitor the long-term effects of HIV infection on the immune system and associated disease sequelae, and on the adverse effects of antiretroviral drugs. Mark Boyd and colleagues, in their Research Article, study patients at elevated risk of cardiovascular and renal disease among more than 27,000 participants in the D:A:D study, and report a multiplicative increase in the risk of events in those patients judged to be at risk of both types of disease.

The issue will continue for the next several weeks with further research and commentary papers—to view the papers, visit the Special Issue Collection.

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Aidspan publishes new issue of ‘Global Fund Observer’ http://www.eatg.org/news/aidspan-publishes-new-issue-of-global-fund-observer-32/ Wed, 08 Nov 2017 22:36:43 +0000 http://www.eatg.org/?post_type=news&p=6732 Aidspan: Global Fund Observer

Aidspan, an independent watchdog of the Global Fund to Fight AIDS, Tuberculosis and Malaria, published Issue 323 of the “Global Fund Observer.” The newsletter includes articles on various topics, including an announcement of a new fund to support the engagement of adolescent girls and young women in Global Fund-related and national processes; a commentary on the Global Fund and PEPFAR’s complementary approaches and collaborations; and a primer on transitioning from Global Fund support.

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HIV remission: the quest to turn lessons from exceptional cases into solutions http://www.eatg.org/news/hiv-remission-the-quest-to-turn-lessons-from-exceptional-cases-into-solutions/ Wed, 08 Nov 2017 22:33:47 +0000 http://www.eatg.org/?post_type=news&p=6731 The case of an HIV-infected child in South Africa who has been in remission for nearly nine years without taking any antiretroviral drugs has provided further proof that HIV remission is possible.

Remission (also known as functional cure) is a term that describes the body’s ability to control HIV to undetectable levels without the use of antiretroviral therapy. Remission refers to a state following treatment that is then stopped. Less than 1% of people who are infected with HIV are naturally able to do this without any treatment.

The South African case – the first reported instance of HIV remission in an African child, and only the third case in the world – has raised many questions: what makes this child so unique? Is it the virus? Is it the host? Were the drugs essential to this outcome?

I am part of a team of researchers that’s investigating this unusual case, an endeavour that’s intensified this year. What we found were signs that HIV can be suppressed naturally for a long time after someone has been on a short spell of treatment. We presented our findings at the 9th International Aids Society conference on HIV science in Paris in July.

The discovery is only the first bit of a puzzle we are piecing together – on an ongoing basis – into what exactly causes suppression. It opens the door for researchers to establish how to make long-term remission possible for other people. This is a critical part of making HIV a manageable disease.

A remarkable outcome

The child – whose gender has not been disclosed – was born in 2007 to an HIV-infected mother. The child was diagnosed as HIV-positive at one month of age and then enrolled in a clinical trial called CHER (Children with HIV Early Antiretroviral Therapy). The trial ran from 2005 to 2011.

The child – randomly selected in the trial to receive early treatment – started anti-retrovirals just after turning two months old. The child was one of 143 babies who received early treatment for 40 weeks.

The virus rebounds within weeks in most people who stop taking the drugs. HIV attacks the T-cells, forcing the person’s CD4 count to drop significantly. But in this instance the child’s CD4 count remained at the level of a healthy child’s after the drugs were stopped. And has remained so ever since.

More than eight and half years later the child has no symptoms of infection. The virus has not rebounded and it cannot be detected with standard methods.

To establish what led to this outcome the child’s blood samples have been subjected to detailed virological, immunological and genetic studies to understand the state of the virus in the body.

The child had high levels of the virus in the blood before starting treatment at two and a half months. This suggested that the child had an actively replicating virus at the time.

But by the time the child was nine and a half years old, there were only small traces of virus in the cells and the virus was no longer actively replicating.

In addition, we saw signs that the child’s immune system had identified the virus before. At this stage we don’t know which parts of the immune system were active close to the time of infection and treatment. Understanding both the response now – and which immune responses were initially involved – is critical to help us develop a vaccine, or other strategies, that could solicit a similar immune response in other people.

What the three rare finds tell us

The three remission cases have provided researchers with different lessons. The first case was a baby born in Mississippi in 2010 who was HIV infected at birth. The baby started treatment 30 hours after she was diagnosed and continued treatment until she was 18-months-old. The virus remained under control – that is below detectable levels – for the next 27 months. But then it rebounded.

This case highlighted that remission was possible for a period of time.

The second case involved a child born in France in 1996. Treatment was started at three-months-old but then stopped when the child was about six years old. The virus remains under control. This case showed that long-term remission is possible.

Our case further confirms that long term remission is possible, even with a short period of treatment.

Since the first remission case, several trials are trying to establish whether starting babies identified with HIV at birth with treatment within 48 hours of the discovery could help.

The thinking is that intercepting HIV as close to the time of infection as possible can result in a smaller reservoir of virus in the cells. This in turn could increase the chances of remission for sustained periods of time or maybe even permanently.

Take home messages

There is no doubt that early treatment is desirable. It reduces chances of transmission, protects the immune system from damage caused by the virus, keeps virus reservoirs small and improves general health and the chances of survival.

But we know that, if treatment is stopped, early treatment isn’t enough for most people to achieve remission. Other interventions need to be sought.

For most infected patients, treatment starts long after they are infected. This presents an even greater challenge to achieve remission.

The South African child tells us that other factors, unique to an individual or to very rare groups of individuals, are important. The clues are there. We need to find what these factors are from the few and turn them into solutions for the many.

And, more important than anything, is that patients don’t stop their treatment until we have all the pieces of the puzzle in place.

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HIV patients at greater risk of both heart and kidney disease http://www.eatg.org/news/hiv-patients-at-greater-risk-of-both-heart-and-kidney-disease/ Wed, 08 Nov 2017 22:31:21 +0000 http://www.eatg.org/?post_type=news&p=6728 HIV patients and their doctors are urged to be more aware of the additional health risks associated with treated HIV infection. This follows new research that shows HIV patients at high risk for a heart attack or stroke are also at substantially greater risk for chronic kidney disease and vice versa.

The research, led by the University of Adelaide’s Professor Mark Boyd, will be published today in a special issue of the journal PLOS Medicine, which focuses on worldwide advances in HIV prevention, treatment and cure in the lead up to World AIDS Day on 1 December.

Professor Boyd, an infectious diseases expert with the Adelaide Medical School, University of Adelaide, led an international team to investigate additional diseases associated with HIV infection and its treatment.

Drawing on data from the international D:A:D (Data collection on Adverse events of Anti-HIV Drugs) study, Professor Boyd and colleagues assessed the risks of cardiovascular disease and chronic kidney disease in people with HIV infection. They found elevated risks of each disease occurring simultaneously.

More than 1400 people in the study being treated for HIV had been diagnosed with chronic kidney disease, and more than 900 had experienced a cardiovascular disease event. Almost 11% of these patients had experienced both chronic kidney disease and cardiovascular disease, with many of these events occurring just one year apart.

“Our research found that people with HIV at high risk of cardiovascular disease had a corresponding 5.63-fold increase in risk of chronic kidney disease — a finding not consistent with the general community,” Professor Boyd says.

“This study adds to the international body of research that shows we need to pay close attention to the broader, general healthcare of people living with HIV.

“It’s wonderful that anti-HIV medication has been able to save the lives of so many with HIV; what we need to do now is to help people with HIV realise the full potential of their much-extended life expectancy.

“Despite much effort over the past decade to focus attention on reducing cardiovascular risk in HIV-positive people, there has been a lack of attention to the management of this disease in people living with HIV. Unfortunately, this has implications for other diseases, and the interaction between diseases creates substantial risks for future life-threatening events,” he says.

Professor Boyd says the research shows that the risks for cardiovascular and chronic kidney disease in people with HIV should be assessed together.

“We strongly urge both people with HIV and their doctors to be aware of these risks, and to treat them as a combined healthcare issue, not separately,” he says.

“Primary prevention and effective management of these diseases, prioritising interventions that have been repeatedly shown in the general community, will convey the same if not greater benefits for the population of HIV-positive people.

“This approach should be incorporated in to the development of guidelines and defining future research priorities for HIV-positive people,” he says.

Professor Boyd has also been invited to participate in the upcoming Clinton Foundation convened Third Conference on Antiretroviral Drug Optimization, 29 November to 1 December, in Johannesburg, South Africa. The event brings together international experts to discuss and debate what is required over the next five years to support the global access to HIV care initiative.

Journal Reference:

  1. Mark A. Boyd, Amanda Mocroft, Lene Ryom, Antonella d’Arminio Monforte, Caroline Sabin, Wafaa M. El-Sadr, Camilla Ingrid Hatleberg, Stephane De Wit, Rainer Weber, Eric Fontas, Andrew Phillips, Fabrice Bonnet, Peter Reiss, Jens Lundgren, Matthew Law. Cardiovascular disease (CVD) and chronic kidney disease (CKD) event rates in HIV-positive persons at high predicted CVD and CKD risk: A prospective analysis of the D:A:D observational study. PLOS Medicine, 2017; 14 (11): e1002424 DOI: 10.1371/journal.pmed.1002424
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Study finds no evidence raltegravir-based ART regimen leads to cancer or death http://www.eatg.org/news/study-finds-no-evidence-raltegravir-based-art-regimen-leads-to-cancer-or-death/ Wed, 08 Nov 2017 22:17:18 +0000 http://www.eatg.org/?post_type=news&p=6730 A crucial step in the propagation of the HIV is the integration of viral nucleic acids into the host genome. This process occurs with the help of the HIV-1 integrase enzyme. Raltegravir is the first approved antiretroviral (ART) drug that works by inhibiting the HIV-1 integrase enzyme, thereby preventing strand transfer. Although raltegravir exhibited satisfactory safety profiles and was approved for use in 2010, increased incidence of cancers was observed in patients who were given a raltegravir-based drug regimen. Recent in vitro data demonstrated that small doses of raltegravir could lead to large rearrangements in the host genome, including insertions and deletions, which would be conducive to developing malignancies.

However, these observations and the in vitro data have yet to be substantiated. A recent study published in HIV Medicine sought to address this question, to determine if raltegravir indeed increases the risk of developing cancer. Co-investigators, Amanda Mocroft, PhD, and Ole Kirk, PhD, led the study.

The authors utilized the EuroSIDA cohort, an on-going prospective study that consists of 18,931 individuals from 111 hospitals in 34 countries currently living with HIV. The cohort was divided into 3 groups: those that started raltegravir-based therapy on or after December 2007, those that added a new antiretroviral drug (not raltegravir) to their regimen between January 2005 and December 2007 (termed HIST), and those that added a new antiretroviral drug (not raltegravir) to their regimen after December 2007 (termed CONC). The raltegravir cohort consisted of 1470 patients, with 4058 person-years of follow-up (PYFU). The other 2 cohorts, HIST and CONC, consisted of 3787 (4472 PYFU) and 4467 (10,691 PYFU) respectively. The authors assessed 4 outcomes: newly diagnosed cancers, both AIDS and non-AIDS related, liver-related events, lipodystrophy, and mortality.

The majority of the patients, across the 3 cohorts, were white males. In addition, the mode of HIV transmission was similar in the 3 cohorts, with 40% of patients being men who have sex with men (MSM). A total of 20% acquired HIV through heterosexual contact, and the remaining patients were persons who inject drugs (PWID).

In the raltegravir cohort, 24% of patients discontinued the drug, with 11% discontinuing the drug within 3 months. These early discontinuations were generally due to raltegravir-related gastrointestinal toxicity or patient choice. The later discontinuations seemed to be mostly due to decisions made by the monitoring physician, with 71 out of the 312 longer-term discontinuations due to this reason.

Overall, the authors found that there was no evidence that the patients in the raltegravir cohort were at increased risk of cancer or death in comparison to those given alternative ART regimens. The study confirms that raltegravir is a safe as a therapeutic option for HIV, particularly for patients who have a history of failed therapy or in patients intolerant towards other ART drugs. However, the authors caution the reader against drawing firm conclusions from the study as it was an observational cohort study and not a randomized clinical trial. In other words, this study is unable to exclude confounding variables, such as lifestyle choices like smoking.

By Samar Mahmoud

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People with HIV more likely to adhere to their antiretroviral therapy than treatment for other chronic health problems http://www.eatg.org/news/people-with-hiv-more-likely-to-adhere-to-their-antiretroviral-therapy-than-treatment-for-other-chronic-health-problems/ Wed, 08 Nov 2017 21:34:20 +0000 http://www.eatg.org/?post_type=news&p=6725

Ageing HIV-positive people have significantly higher levels of adherence to their antiretroviral therapy than to medication taken for other chronic health problems, Swiss investigators report in HIV Medicine. The research also revealed that people living with HIV rated the necessity of their HIV treatment more highly than therapy for other illness and also had lower levels of concern about their antiretroviral treatment compared to therapy for co-morbid conditions.

“This is the first study on HIV-infected patients’ beliefs about all their co-treatment in comparison with their cART [combination antiretroviral therapy],” comment the investigators. “It is essential to explore the different beliefs about medicines of comorbid HIV-infected patients which may influence their medication management strategies and decisions to adhere to prescribed regimens.”

The success of antiretroviral therapy means that most HIV-positive people now have an excellent life expectancy. People living with HIV can expect to survive well into old age and therefore require treatment for chronic health problems such as cardiovascular disease, osteoporosis and depression.

Investigators from the Swiss HIV Cohort hypothesised that people would have differing attitudes towards their HIV treatment and therapy taken for other conditions.

They therefore designed a prospective, observational cross-sectional study involving antiretroviral-treated people taking long-term therapy for at least one other chronic health problem. After a routine clinic visit, individuals were asked to complete two standardised questionnaires assessing beliefs about the necessity of their treatment and their concerns about such therapy. The first questionnaire explored beliefs about antiretroviral treatment, the second beliefs about therapy taken for other chronic conditions.

Concerns were rated on a scale from 1 (low) to 5 (high).

Adherence to HIV therapy and treatment was also measured. Adherence was defined as not missing any doses in the previous four weeks.

The survey took place between 2015 and 2016.

The final study sample consisted of 105 people. Three-quarters were men and the median age was 56 years. Half the participants were employed and 26% had a bachelor’s degree or higher. Almost all (97%) had an undetectable viral load and median CD4 cell count was 707 cells/mm3. The major prescribed co-therapies were for cardiovascular disease (79%) and depression (44%).

A significantly higher proportion of people reported being adherent to their HIV treatment compared to therapy for co-morbidities (87 vs 75%, p = 0.0001).

The necessity of antiretroviral therapy was rated much higher than treatment for other chronic health problems (mean scores: 4.46 vs 2.86, p < 0.0001). Individuals without a university degree gave higher scores for co-treatment necessity than those with a degree.

“This counterintuitive result might be a consequence of patients with more education possibly being more likely to question their doctors’ decisions regarding co-treatment choices and believing that they know their disease and treatment options well, and are capable of making educated decisions about their therapy,” suggest the authors.

Overall, patients were more likely to be concerned about their co-medications than their HIV therapy (mean scores: 4.09 vs 2.9, p < 0.001).

Taking two or more co-medications was associated with higher necessity scores (p = 0.041) and increased concerns (p = 0.036). A higher CD4 cell count was associated with a higher co-treatment necessity score (p = 0.016).

“Further research is needed to explore the association between adherence and patients’ perceptions,” conclude the authors. “Although our findings need confirmation, they suggest that it could be important to focus on patient beliefs to improve adherence to co-treatments.”

By Michael Carter

Reference

Kamal S et al. HIV-infected patients’ beliefs about their chronic co-treatments in comparison with their combined antiretroviral therapy. HIV Med, online edition. DOI: 10.1111/hiv.12542 (2017).

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HIV diagnoses in English gay men have been falling since 2014 http://www.eatg.org/news/hiv-diagnoses-in-english-gay-men-have-been-falling-since-2014/ Wed, 08 Nov 2017 21:31:02 +0000 http://www.eatg.org/?post_type=news&p=6723

A new analysis by Public Health England of testing rates and HIV diagnoses from all of England’s sexual health clinics shows that the decline in diagnoses is England-wide, started at least a year before the decline was first noticed at London’s 56 Dean Street clinic, and is not restricted to gay men who test frequently.

One of the big stories in HIV prevention this year has been the dramatic drop in HIV diagnoses being seen among gay men in HIV clinics in London. This started when, less than a year ago, Dean Street clinic announced a 40% drop in infections in 2016. This trend, there and at other inner London clinics, has been maintained to the extent that there were only four HIV diagnoses at Dean Street in October 2017 compared with 60 in October 2015 – a drop of 93%.

However Noel Gill of Public Health England, presenting data from English sexually transmitted infection (STI) clinics at the recent 16th European AIDS Conference (EACS 2017) in Milan, said that there was evidence that the falls in HIV diagnoses had started earlier and were national.

In summary, HIV diagnoses have fallen by 65% in London and by 48% outside London from their peak in 2014. In the third quarter of 2014 there were approximately 370 HIV diagnoses in gay men in London and 250 outside. They then started to fall, and in the second quarter of 2017 the total of new HIV diagnoses both in and outside London was 130. The decline was already well underway in London by mid-2016, which is when Dean Street noticed it. London HIV diagnoses in the second quarter of 2016 had already fallen by 46% relative to their peak in 2014.

What has caused the decline in diagnoses? Noel Gill did not ascribe it to any one cause, but said that the “lower threshold of access to HIV testing” with results available within an hour and the use of self-sampling and, increasingly, self-testing as options were all helping. He also said it was important that STI clinics in the UK were generally “held in high regard” by their users.

An increase in attendances and in the frequency of HIV testing among gay men are associated with the declines in diagnosis.

Starting in 2014, there was a large increase in the number of attendances at STI clinics by gay men and in the frequency of HIV testing. There were 14,500 attendances by gay men at high risk of HIV in London clinics in the first quarter of 2014. This expanded, within 18 months, to about 19,000 attendances and has stayed at that level since. Out of London, the increase took longer, but there were over 14,000 attendances per quarter by the third quarter of 2016, up from 10,000 in early 2014.

The number of attendees who were classed as “frequent testers” increased in London from 6400 in the first quarter of 2014 to 9700 in the first quarter of 2015 and then stayed at that level. Again, the increase was slower to take hold outside London but increased from 4000 in the first quarter of 2014 to 6000 in the first quarter of 2016.

The quarterly number of HIV tests among frequently testing gay men increased from roughly 3500 per quarter in 2012 to over 8200 in 2017 and in men who tested less frequently from about 4500 to about 7000. However, the number of tests in the less-frequent testers has stayed at that level since early 2015 and may even have fallen slightly. This may indicate that there needs to be new encouragement for frequent testing among gay men who are not aware of the importance of testing frequently, or who are not at high risk or do not see themselves as ‘high risk’.

This is especially important as there were more HIV diagnoses among the less-frequent testers than among the frequent testers. This may seem counter-intuitive, but frequent testers are presumably more health-conscious, and may already belong to networks where most of the HIV-positive people are diagnosed and on HIV treatment. Or, because tests are spaced more widely in infrequent testers, the proportion of results that are positive are higher, simply because more time has elapsed. And finally, ‘infrequent testers’ includes ‘first testers’ – a proportion of the diagnoses are late diagnoses in people infected years ago.

Whatever the reason, the quarterly number of diagnoses in frequently testing gay men averaged about 40 in 2012, increased to 70 in 2014-15 and then decreased again to 40 in 2016.

In infrequent testers there were more diagnoses, but the decline in diagnoses was also more marked. They averaged 150 per quarter in 2012-13, increased to about 200 a quarter in 2014, but started to decline from mid-2015 onwards and in the second half of 2016 were only averaging 80 per quarter.

The public health significance of frequent testing is only fully realised if people who are diagnosed start antiretroviral therapy (ART) as soon as possible, as reducing the time spent between infection and viral suppression is the most critical factor in bringing down HIV transmission.

In 2012, the time taken until half of those diagnosed were on ART was 1.2 years and until 90% were on ART was 3.6 years. By 2014 this had been reduced to 3 months and 1.9 years respectively. The latest figures, from 2016, show that 50% of people diagnosed are on ART within a month and 90% within 3 months.

So far, Gill said, the three most important factors contributing to the observed decline were:

  • A 50% increase in STI clinic attendance in gay men since 2011
  • An increase in the frequency of gay men’s HIV testing, with the average now 2.5 tests a year
  • Putting 90% of those diagnosed with HIV on treatment within less than a year.

He did not speculate on whether there was an additional role for pre-exposure prophylaxis (PrEP), as the decline in diagnoses started happening before its more widespread availability. However, PrEP may have subsequently accelerated the decline in the inner-London clinics, as the rate of decline in clinics like Dean Street and Mortimer Market is both more recent and steeper than that seen in the Public Health England data. San Francisco is another example of a city where HIV diagnoses were already declining but where the rate of decline increased after clinic attendees started using PrEP.

By Gus Cairns

Reference

Gill N. What is happening with new HIV diagnoses in gay men in England and why? Mini-Lecture no ML3, Session PS11, Understanding our Evolving Epidemic. 16th European AIDS Conference, 25-27 October, Milan, 2017.

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High HIV incidence from non-primary partners and low PEP and PrEP use seen in PARTNER study http://www.eatg.org/news/high-hiv-incidence-from-non-primary-partners-and-low-pep-and-prep-use-seen-in-partner-study/ Wed, 08 Nov 2017 21:26:22 +0000 http://www.eatg.org/?post_type=news&p=6722

HIV incidence among the HIV-negative gay men in the PARTNER 1 and 2 studies, due to sex with partners outside the main relationship, was high, and very high in partners who admitted having condomless anal sex with non-primary partners, the 16th European AIDS Conference (EACS 2017) heard recently.

The conference heard that even now, in the latest data from the PARTNER 2 study, only 5% of HIV-negative participants are taking pre-exposure prophylaxis (PrEP), even though over a third have had condomless anal sex with non-primary partners.

The data were presented by Valentina Cambiano of University College London, who is one of the investigators in the PARTNER studies.

PARTNER is arguably one of the most significant HIV prevention studies ever conducted. It studies couples where one partner has HIV and the other does not and its primary aim is to try to quantify the risk of transmission from a person on HIV treatment who has a fully suppressed viral load. While enrolment of heterosexual couples stopped at the end of PARTNER 1 in 2014, it was decided more data on gay men was needed so PARTNER 2, for gay couples only, is still underway.

PARTNER made headlines when in 2014, and again in 2016, the researchers confirmed that there had been no transmissions from an HIV-positive partner who was on antiretroviral therapy and virally suppressed in, by 2016, an estimated 58,213 condomless sex acts. These data allowed the researchers to establish the maximum possible likelihood of transmission, and to announce that, most likely, the chance of an HIV-positive partner with a fully suppressed viral load of below 200 copies/ml passing on HIV was zero, or statistically indistinguishable from it.

PARTNER, and other studies like Opposites Attract and HPTN 052, have provided the evidence base for the success of ‘Treatment as prevention’ and for the U=U (Undetectable = Untransmittable) campaign.

However, there were HIV infections in PARTNER: eleven of them by 2016, ten in gay men. In all cases, however, phylogenetic testing showed that the infecting virus came from someone other than the primary partner. Eight of the eleven infected people told researchers they had had condomless sex with partners other than their primary partner: the other three must have done too.

Cambiano told the conference that multiplying the number of infections by the amount of time people were in follow-up before infection leads to an estimated HIV incidence of 2.3% a year – quite high. However, if only the eight men who admitted to having condomless anal sex with other partners are counted, then incidence becomes very high – 7.2% a year, or higher than that seen in the placebo arm of the IPERGAY PrEP trial.

In short, just because your main partner is undetectable, it does not mean you are safe from HIV if you have condomless sex elsewhere. In these cases, it would make sense to use post-exposure prophylaxis (PEP) or PrEP – but how many in PARTNER were doing so?

Cambiano and colleagues studied PEP and PrEP use in the 737 HIV-negative partners who had answered both the baseline sexual behaviour questionnaire and a questionnaire on at least one follow-up visit.

They had been in the study on average 1.6 years and had averaged one year of condomless anal sex with their primary HIV-positive partner. Thirty-five per cent said they had had condomless anal sex with other partners and 22% had been diagnosed with a sexually transmitted infection other than HIV. The researchers estimated that on average they had 35 acts of condomless anal sex per year with other partners. They also worked out that the total number of condomless anal sex acts with main partners now amounted to 69,098 acts, strengthening the conclusion that HIV transmission is not taking place when the main partner has undetectable viral load.

At baseline, in both phases of the study, over one in six men (17.5% in PARTNER 1 and 17.9% in PARTNER 2) had ever taken PEP. But far fewer had ever taken PrEP; only 1.5% in PARTNER 1 and 3.9% in PARTNER 2. This is not that surprising as PARTNER is a mainly European study, and PARTNER 1 recruited in 2010 and PARTNER 2 in 2014.

During the studies a further 3% in PARTNER 1 and 4.6% in Partner 2 used PEP, and 3% and 5% used PrEP. This means that in PARTNER 2 8.2% of the HIV-negative partners used PEP and/or PrEP.

However, if the partners admitted to having had condomless anal sex with other men in the follow-up questionnaire, then they were twice as likely to have used PEP and three times as likely to take PrEP: 8.7% of these men took PEP and 10.3% were using PrEP, meaning that nearly 16% had used PEP and/or PrEP.

The 10.3% using PrEP numbered 253 men. A majority (58%) were in the UK, with smaller numbers in other countries: 11% each in France and Switzerland, 8% each in Germany and the Netherlands, and 4% in Spain.

This finding meant that in men reporting condomless anal sex with outside men, PEP or PrEP only covered 12% of sex acts that risked HIV infection and only 1.5% of acts in men who did not report it. It can easily be seen that if the negative partners had covered, say, 80% of their possibly risky sex acts with PEP or PrEP instead of 16%, then HIV incidence would have been considerably lower.

Valentina Cambiano commented that the low level of PEP and PrEP use and the high HIV incidence seen from sex outside the main relationship were of concern.

“PrEP eligibility discussions with HIV-negative MSM [men who have sex with men] should ensure that risks from all sexual contacts are taken into consideration, and routes to securing PrEP discussed,” she added.

By Gus Cairns

Reference

Cambiano V et al. Use of PEP and PrEP among HIV Negative MSM in the PARTNER Study. 16th European AIDS Conference, 25-27 October, Milan, abstract PS11/4, 2017.

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European AIDS Clinical Society strengthens HPV vaccination advice http://www.eatg.org/news/european-aids-clinical-society-strengthens-hpv-vaccination-advice/ Wed, 08 Nov 2017 21:17:59 +0000 http://www.eatg.org/?post_type=news&p=6721 New European guidance responds to growing evidence of anal cancer risk in HIV-positive men who have sex with men

The European AIDS Clinical Society (EACS) has recommended HPV (human papillomavirus) vaccination for everyone living with HIV aged under 26 and all men who have sex with men up to the age of 40.

HPV is a sexually transmitted virus that causes genital warts, and in some forms, leads to the development of cervical, anal and oropharyngeal cancers. Anal cancer, rare in the general population, is becoming more common in people living with HIV, especially men who have sex with men.

HPV vaccination

Deborah Konopnicki of St Pierre University Hospital, Brussels presented a review of the evidence supporting vaccination against HPV in people living with HIV at last month’s 16th European AIDS Conference (EACS 2017) in Milan.

Screening for HPV-related cancers is inconsistent and for anal cancer, the choice of screening technique is still a matter of debate, she said. As for oropharyngeal cancers caused by HPV, whether to screen for these conditions is still unclear.

Greater use of preventive vaccines has the potential to reduce HPV-associated morbidity. Vaccination of girls and young women has resulted in significant reductions in HPV-associated morbidity in Australia, Denmark and Scotland, within ten years of the first vaccination programmes.

Only one study, the ACTG 5298 study, has looked at the effect of vaccination on protection against HPV infection in HIV-positive adults. That study found that in a predominantly male population with a median age of 47 years vaccination did not reduce persistent infection with HPV.

This finding led EACS to recommend that HPV vaccination should be offered to people with HIV aged 26 and under. EACS has also followed the British HIV Association in recommending vaccination for all men who have sex with men with HIV under the age of 40. Previous guidance issued in 2015 recommended that doctors should follow national guidance on HPV vaccination.

Although EACS states that the efficacy of the vaccine is questionable in people who have already been exposed to HPV, Deborah Konopnicki said it is still plausible that vaccination could improve protection against HPV-associated disease.

The ACTG A5240 study showed that in women already seropositive for any of the HPV types included in the quadrivalent vaccine, vaccination resulted in a substantial increase in HPV antibody titres (levels) (+1.5 log10 IU/ml).

There is also some evidence from studies in HIV-negative women and men who have sex with men that vaccination after the treatment of HPV-associated cervical or anal lesions is associated with reductions in recurrence of lesions. Two ongoing studies are likely to provide further information on vaccination’s role in the prevention of recurrence in people living with HIV.

Vaccination results in greater antibody responses in women living with HIV who already have undetectable HIV viral load at the time of the first vaccination, probably because viral suppression permits immune restoration.

EACS recommends the 9-valent HPV vaccine if available (active against nine common types of HPV). Dr Konopnicki noted that there is no evidence in people living with HIV to support anything less than a 3-dose vaccination schedule, although several studies in young women have shown that a single vaccination is just as immunogenic as multiple vaccinations.

Anal cancer

Research from Austria presented at the conference by Robert Zangerle of the Medical University, Innsbruck, showed that by 2015, anal cancer had already affected at least one in forty men who have sex with men receiving care in clinics affiliated to the Austrian HIV Cohort Study. Dr Zangerle said that the rate was already “alarmingly high”.

The cohort covers around three-quarters of people receiving HIV care in Austria (7511 people). Between 2003 and 2015, 46 cases of anal cancer were diagnosed, 63% in men who have sex with men. The overall incidence was 52.5 cases per 100,000 person-years of follow-up but was higher in men who have sex with men (95.1 per 100,000 person-years) and lower in women (36.5 per 100,000 person-years).

By 2015, 0.8% of men who have sex with men in care who were under the age of 50 had ever been diagnosed with anal cancer, but the cumulative prevalence rose to 2.6% in men who have sex with men over the age of 50 and 1.6% in women with HIV aged 50 and over. In summary, the Austrian cohort study found that one in forty men who have sex with men with HIV aged 50 and over had already been diagnosed with anal cancer, and the median age of the over-50 age group was 56 years, suggesting that anal cancer could continue to be a significant cause of disease as men age.

By Keith Alcorn

References

Konopnicki D et al. HPV vaccination: who to vaccinate, which vaccine to use, how to evaluate the success of vaccination. 16th European AIDS Conference, 25-27 October, Milan, mini-lecture 3, 2017.

Zangerle R et al. The incidence rate of anal cancer in the Austrian HIV Cohort Study. 16th European AIDS Conference, 25-27 October, Milan, abstract PS7/2, 2017.

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HIV patients live longer, require intricate geriatric care http://www.eatg.org/news/hiv-patients-live-longer-require-intricate-geriatric-care/ Wed, 08 Nov 2017 21:04:29 +0000 http://www.eatg.org/?post_type=news&p=6720 DALLAS – HIV adds to the typical health concerns that affect people as they age, and with fewer people dying of AIDS, healthcare providers are facing more complicated geriatric cases.

By 2030, 73% of people with HIV will be older than 50 years, according to one report (Lancet Infect Dis. 2015;15:753-754). But despite advances in antiretroviral therapy, life expectancies are still lower for people with HIV than for those without, according to a population-based study (J Acquir Immune Defic Syndr. 2016;71:213-218).

One of the key issues of concern for people with HIV is that they will develop more comorbidities as they age than uninfected people, said Kristine Erlandson, MD, from the Divisions of Infectious Diseases and Geriatric Medicine at the University of Colorado Hospital in Aurora.

Polypharmacy, which is already common in older patients, is an even greater issue in people with HIV because of their added comorbidities. And it can lead to a host of health problems.

The Problem of Polypharmacy

“We know that more medications are associated with decreased drug adherence, an increased risk of drug side effects, increased drug-to-drug interactions, and a risk for geriatric syndromes, including falls, cognitive impairment, and frailty,” Dr Erlandson said here at the Association of Nurses in AIDS Care (ANAC) 2017.

The use of five or more medications is associated with increased mortality in older adults, but the association is stronger in people with HIV, according to data from one cohort of veterans (Drugs Aging. 2013;30:613-628).

And a recent review of 248 older San Franciscans with HIV – presented by Meredith Greene, MD, from the UCSF School of Medicine in San Francisco at the 8th International Workshop on HIV & Aging in October – showed that patients were taking a mean of 14 medications, 11 of which were not related to HIV.

Alarmingly, 16% of the patients were taking more than 20 medications, and 63% were taking at least one potentially inappropriate medication, Dr Erlandson reported.

“This is clearly a huge problem in the geriatric population of HIV-positive patients,” she pointed out.

The best strategy to address polypharmacy is to enlist the help of the pharmacist.

“Have your patients take all of their medications, including supplements, over-the-counter medications, ointments, nasal sprays, eye drops – everything – to the pharmacist, who can help sort things out,” she advised. And, she added, recommend that patients use a single pharmacy for their HIV care.

When a patient presents with a complaint, clinicians should explore whether the symptoms are an adverse drug effect, a drug-drug interaction, or an underlying medical problem, Dr Erlandson said.

One resource for the latest information on drug interactions is the Beers Criteria for Inappropriate Medication Use in the Elderly, from the American Geriatrics Society, she added.

Bone Health

Bone loss is a common problem in older patients with HIV. The risk for osteoporosis that can be up to 3.7 times higher in infected than uninfected people, she reported.

Clinicians might want to avoid antiretroviral regimens that contain tenofovir disoproxil fumarate and instead use a combination of abacavir and lamivudine or tenofovir alafenamide and emtricitabine, she said.

Patients should also be evaluated for other possible contributors to osteoporosis, such as low testosterone level, low vitamin D level, phosphate wasting, hyperparathyroidism, substance use, and smoking.

Because of the increased risk for osteoporosis in older people with HIV, the risk for fracture is also elevated. The Partners HealthCare System study, which included 8525 people infected with HIV and more than 2 million uninfected people, showed that after the age of 50, fractures are significantly more common in women (P = .002) and men (P < .0001) with HIV than in those without ( J Clin Endocrinol Metab. 2008;93:3499-3504).

Falls are the cause of many, if not most, fractures. In a study of 359 HIV-positive patients conducted by Dr Erlandson and her colleagues, 30% had fallen at least once in the previous year, and 18% had fallen more than once (J Acquir Immune Defic Syndr. 2012;61:484-489).

The key risk factors for falls were difficulty completing a tandem stand, defined as standing with one foot directly in front of the other, heel to toe, for 10 seconds without stumbling (odds ratio [OR], 13.5), antidepressant use (OR, 3.7), exhaustion (OR, 3.7), diabetes (OR, 3.6), and being female (OR, 3.5).

Fall prevention measures – including discontinuing medications that contribute to dizziness and exercising to improve balance and strength – can make a difference. “Tai chi has been shown to have particular benefit in some studies,” Dr Erlandson noted.

Exercise can also help manage the weight gain that is associated with antiretroviral therapy and that may contribute to comorbidities such as fatty liver and diabetes, she explained.

Adults with HIV can also experience muscle loss accompanied by generalized weight gain, leading to sarcopenic obesity. “Treatment should focus on reducing weight through dietary change and increasing muscle mass through exercise and adequate protein to maximize function,” she said.

Frailty

Clinicians are probably used to resistance from patients when it comes to exercise recommendations, but they should keep in mind that older patients with HIV face unique challenges, such as greater perceived or actual fatigue, said Dr Erlandson.

Patients can feel stigmatized by their HIV status and have difficulty adopting a long-term perspective on health and wellness. And they might be in various stages of frailty, which often is “easy to recognize but hard to define,” she pointed out.

The Rockwood Index and other tools can help identify frailty, but it is important to remember that it is a “multisystem clinical syndrome that reflects biologic rather than chronologic age and a vulnerability to stressors,” she said.

The recent observational HAILO study showed that 6% of HIV-positive men and women aged 40 years and older were frail (AIDS. 2017;31:2287-2294). The risk for recurrent falls was more than 17 times greater in frail than in nonfrail patients.

“Knowing frailty status can provide an excellent assessment of fall risk,” Dr Erlandson said.

Other research has shown that early intervention can significantly help frail patients.

In general, frail patients tend to have greater responses to multidomain interventions that include elements such as exercise, nutritional counseling, and ― as some studies suggest ― vitamin D supplementation and hormone replacement.

The care of HIV patients needs to be better coordinated, said Veronica Njie-Carr, PhD, from the University of Maryland School of Nursing in Baltimore.

In a focus group conducted at her center, patients discussed the fact that HIV practitioners should be trained in geriatric medicine, Dr Njie-Carr reported.

“This presentation validates that at the patient level,” she noted.

“The patients also expressed how they have to go to one practitioner for their renal problem and another for arthritis, etc. So there clearly is the need for better coordination of care,” she added.

Dr Erlandson reports receiving funding from the National Institutes of Health National Institute on Aging and research funding or speaker fees, paid to the University of Colorado, from Gilead Sciences and Theratechnologies. Dr Njie-Carr reports no relevant financial relationships.

Association of Nurses in AIDS Care (ANAC) 2017. Presented November 3, 2017.

By Nancy A. Melville

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Promising new drug for hepatitis B tested http://www.eatg.org/news/promising-new-drug-for-hepatitis-b-tested/ Wed, 08 Nov 2017 21:02:20 +0000 http://www.eatg.org/?post_type=news&p=6718 Promising new drug for hepatitis B tested at Texas Biomedical Research Institute

San Antonio, Texas (November 7, 2017) – Research at the Southwest National Primate Research Center (SNPRC) on the campus of Texas Biomedical Research Institute helped advance a new treatment now in human trials for chronic hepatitis B virus (HBV) infection. Testing at SNPRC provided proof this novel therapeutic approach and drug delivery mechanism would be safe and effective, as recently published in the international journal Science Translational Medicine.

The World Health Organization characterizes hepatitis B as a major global health problem. An estimated 250 to 400 million people are chronically infected with the virus. More than 800,000 people a year die from complications of cirrhosis of the liver and liver cancer. A vaccine that is 95% effective in preventing hepatitis B infections has been available since 1982, but there is currently no cure for the millions already chronically infected.

The novel therapy by Arrowhead Pharmaceuticals uses a mechanism called RNA interference to reduce the surface antigens created by chronic HBV infections. Surface antigens (called HBsAg) are small molecules involved in virus entry into liver cells. In chronic infection, they may prevent the immune response from clearing the virus. For example, a high level of HBsAg can lead to a greater risk of long-term, chronic infection with hepatitis B and life-threatening complications like cirrhosis and liver cancer. In this setting, reducing HBsAg by RNA interference will have beneficial effects.

Much of the groundbreaking work lies in the technology Arrowhead developed for delivering this small interfering RNA precisely to the liver. Experiments involving chimpanzees at the SNPRC from 2013-2015 provided the proof that this technology works and is safe for humans, laying the groundwork for the patient clinical trials that have followed. Trials of targeted HBV intervention in non-human primates showed the experimental drug was safe and effective enough to be tested in people.

The Director of the SNPRC, Robert Lanford, Ph.D., explained this novel treatment — in combination with conventional HBV therapy — could empower the immune system to kill the HBV-infected cells and potentially cure people of the disease.

“We now have a drug that can knock down hepatitis B surface antigen and determine whether or not we can actually cure people with that,” Dr. Lanford said.

The drug is delivered by subcutaneous (under the skin) injection. Scientists designed a molecule that delivers the medicine directly to the liver where it binds to a receptor. Then, another molecule that’s derived from bee venom, helps break through membranes in the liver cells to deliver the medicine directly into the cytoplasm of the cells where it takes effect. The siRNA interferes with the expression of the HBV messenger RNA that produces the surface antigen.

“The idea is if you could knock the levels of surface antigens down far enough, the immune system would kick back in,” Dr. Lanford said. “This technology is pretty specific for the liver right now, but there are a lot of problems in the liver that you can fix with this besides hepatitis B.”

This kind of targeted therapy may someday be used to develop drugs for other chronic liver conditions like a genetic disorder called Alpha-1 antitrypsin deficiency, caused by mutated inherited genes, which can cause cancer.

The paper outlining the phase two clinical trials in people and the previous studies involving non-human primates was published in the September 27, 2017 edition of the journal Science Translational Medicine, an interdisciplinary medical journal established by the American Association for the Advancement of Science.

Although the SNPRC no longer uses chimpanzees for biomedical research, studies conducted with these non-human primates over decades continue to yield significant scientific information that will advance human health.

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Texas Biomed, formerly the Southwest Foundation for Biomedical Research, is one of the world’s leading independent biomedical research institutions dedicated to advancing health worldwide through innovative biomedical research. The Institute is home to the Southwest National Primate Research Center (SNPRC) and provides broad services in primate research. SNPRC contributes to a national network of National Primate Research Centers (NPRCs) with specialized technologies, capabilities and primate resources, many of which are unique to the SNPRC. The Center also serves investigators around the globe with research and technical procedures for collaborative projects. For more information on Texas Biomed, go to www.TxBiomed.org or for more information on SNPRC, visit www.SNPRC.org.

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit www.arrowheadpharma.com.

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Scratching the surface of mature monocytes…and coming up with CXCR7 http://www.eatg.org/news/scratching-the-surface-of-mature-monocytes-and-coming-up-with-cxcr7/ Wed, 08 Nov 2017 20:16:28 +0000 http://www.eatg.org/?post_type=news&p=6719 New research in the Journal of Leukocyte Biology reveals potential therapeutic target to reduce brain inflammation in disease

New research published online in the Journal of Leukocyte Biology showed for the first time that mature monocytes (a specific type of white blood cell) express the CXCR7 receptor on their surface. This receptor may be a therapeutic target for controlling inflammation in the brain associated with diseases like multiple sclerosis, Parkinson’s and AIDS.

“Since mature monocytes appear to be the only white blood cells that primarily use CXCR7 to respond to the CXCL12 brain stimulus, we may have hit upon a novel method to block inflammation and HIV infection in the brain,” said Mike Veenstra, a researcher involved in the work from the Departments of Pathology, and Microbiology and Immunology, at Albert Einstein College of Medicine in Bronx, New York. “We hope our findings spur further research and development of targets against the receptor so that novel treatment for NeuroAIDS and other diseases can become readily available.”

To conduct the experiment, Berman and colleagues obtained cells from the peripheral blood of HIV-negative and HIV-infected individuals. Within these cells, the researchers examined the surface receptors CXCR4 and CXCR7 that were expressed on mature monocytes. They then performed blocking studies with pharmacological agents against each of the receptors using a tissue culture model of the human blood brain barrier to determine which of the surface receptors was used to enter the brain.

“Migration of blood monocytes to the brain can be involved in many diseases, including autoimmunity and spread of infections like HIV to the brain,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “These new findings might provide a novel approach to prevent these ‘Trojan horses’ in the cases of HIV from transporting their payload to the brain.”

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The Journal of Leukocyte Biology publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.

Details: Mike Veenstra, Dionna W. Williams, Tina M. Calderon, Kathryn Anastos, Susan Morgello, and Joan W. Berman. Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS. J Leukoc Biol November 2017 102:1173-1185; doi:10.1189/jlb.3HI0517-167R ; early online: July 28, 2017, final version: Nov. 1, 2017 ; http://www.jleukbio.org/content/102/5/1173.abstract

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Clues to body’s defense against common oral ailment http://www.eatg.org/news/clues-to-bodys-defense-against-common-oral-ailment/ Wed, 08 Nov 2017 20:14:38 +0000 http://www.eatg.org/?post_type=news&p=6729 An international team, led by researchers at the University of Pittsburgh School of Medicine, has identified the mechanism by which the immune system first learns that the fungus Candida albicans, which causes oral thrush, has invaded the body. The culprit is a fungal toxin called Candidalysin, which punches holes in cells lining the mouth and is sensed by the immune system, which then begins to mount a defense.

The new findings, published today in the journal Science Immunology, could eventually lead to better treatments for oral thrush, which can produce pain severe enough to cause difficulty eating and swallowing, as well as other fungal infections.

The mouth is home to a large number of microbes, termed commensals, which are harmless in healthy individuals. However, suppression of the immune system can lead to severe and reoccurring painful oral infections from these organisms, explained the study’s co-senior author Sarah Gaffen, Ph.D., who holds the Gerald P. Rodnan Endowed Chair in the Division of Rheumatology & Clinical Immunology at Pitt.

One such example is the fungus Candida albicans. The harmless commensal form exists as a small single-celled organism, but when the immune system is compromised, Candida elongates into an invasive form, characterized by long filaments called hyphae, that causes a pervasive infection called oral candidiasis, or “thrush.”

The immature immune systems of infants make them particularly susceptible to thrush, which can lead to a failure to thrive and nutritional deficiencies. The infection also is prevalent among HIV/AIDS patients, denture wearers and those on immunosuppressants, including chemotherapy and drugs to prevent the rejection of transplanted organs. In fact, at least 50 percent of HIV patients struggle with repeated thrush infections.

However, surprisingly little is known about how fungal immunity in the mouth operates, and, until now, it was unclear why Candida does not establish an invasive infection in healthy humans, said Gaffen.

Her lab previously showed that an immune hormone called interleukin-17 (IL-17) and the specific cells that make it — a subclass of immune cells called helper T cells — are essential to immunity against oral thrush.

Oral epithelial cells (OECs), which are part of the mucous membrane lining the inside of the mouth, are the first cells in the body to encounter Candida. They ignore the yeast until it begins to grow hyphae, at which point the OECs stimulate helper T cells to produce IL-17.

In the new study, the researchers used a combination of human OECs cultured in laboratory dishes and mice infected orally with Candida, to show the central importance of Candidalysin, a toxin secreted by Candida that allows the fungus to create holes in OECs and invade the tissue. Further experiments revealed that IL-17 and Candidalysin act in a synergistic manner to amplify antifungal signals in cultured OECs.

Candidalysin was discovered in 2016 by the study’s other co-senior author, Julian Naglik, Ph.D., professor of fungal pathogenesis and immunology, King’s College London, United Kingdom.

“To use a Game of Thrones analogy: the oral epithelial cells form a protective ‘wall’ that keeps the marauding Candida invaders at bay. Patrolling the wall are the helper T cells, which use IL-17 as their weapon to protect the kingdom,” said the paper’s first author, postdoctoral fellow Akash Verma, Ph.D.

Despite millions of fungal infections worldwide, there are no commercially available anti-fungal vaccines. “Our research provides vital clues to understand the immune defense network at barrier sites of the body. This knowledge may ultimately be harnessed to design antifungal vaccines,” Gaffen said.

Journal Reference:

  1. Akash H. Verma et al. Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Science Immunology, 2017 DOI: 10.1126/sciimmunol.aam8834
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ACHIEVE Coalition sends open letter to Romanian MoH http://www.eatg.org/news/achieve-coalition-sends-open-letter-to-romanian-moh/ Tue, 07 Nov 2017 22:59:07 +0000 http://www.eatg.org/?post_type=news&p=6699 The ACHIEVE Coalition sent this open letter to the Minister of Health of Romania today. The letter, co-signed by EATG as a member of ACHIEVE, calls the Romanian government to prioritise viral hepatitis in health policies of the European Union when acting as the President of the EU Council in 2019.

“Your support would be invaluable in helping the European Union, its Member States and countries across Europe to deliver on their commitments to eliminate hepatitis B and C by 2030 as set out in the WHO Global Strategy and WHO Europe Action Plan. Action in this area will also complement implementation of the EU’s UN Sustainable Development Goals’ (SDG) commitments to end the epidemics of AIDS, tuberculosis and combat hepatitis” – states the open letter.

Read the full letter here: 171107 ACHIEVE letter Minister Bodog on priorities for Romanian Council Presidency

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Worldwide 52 million children living with viral hepatitis http://www.eatg.org/news/worldwide-52-million-children-living-with-viral-hepatitis/ Tue, 07 Nov 2017 22:55:59 +0000 http://www.eatg.org/?post_type=news&p=6706 New data presented at this year’s World Hepatitis Summit in Sao Paulo, Brazil (1-3 November) show that 52 million children are living with viral hepatitis worldwide, compared to 2.1 million children living with HIV/AIDS.

An estimated 325 million people were living with viral hepatitis worldwide in 2016. Of these, 4 million were children living with hepatitis C (under 19 years) and 48 million (under 18 years) were children living with hepatitis B. Both viruses can lead to liver disease, liver cancer and deaths.

“Children are suffering a huge burden of viral hepatitis worldwide, and the public health implications of this are enormous,” says Raquel Peck, CEO of World Hepatitis Alliance. “Most infected infants and children are not diagnosed, prioritised or treated effectively.”

According to new analysis on hepatitis C in children, from Manal El-Sayed, Professor of Pediatrics at Ain Shams University, Cairo, Egypt, and Dr Homie Razavi and his team from the Polaris Observatory, the Center for Disease Analysis (CDA) Foundation, Lafayette, CO, USA, just 21 countries* are responsible for around 80% of these pediatric hepatitis C infections, with the highest prevalence rates generally found in developing countries.

Mother to Child Transmission is one of the main causes of hepatitis C in children. However, neither pregnant women nor young children with this cancer-causing illness can be treated with the highly-effective direct-acting antiviral (DAA) medications. Various regulatory agencies such as the US FDA and the European Medicines Agency have now approved DAAs for use in children aged 12 years and over*. But in high-income countries, there is as yet little evidence they are being used in this age group. WHO is also yet to recommend DAA in any children regardless of age.

As a result, almost all children are only treated with older pegylated interferon regimens, which often have severe side effects including stunting growth, influenza-like symptoms, anaemia and weight loss, and do not always cure the virus. Trials of DAA drugs in children under 12 years are also ongoing, but they have not been approved yet in any country for these younger children.

“Currently, 4 million children are living with hepatitis C, which can be cured and 48 million with hepatitis B, which has a vaccine”, said Charles Gore, President of the World Hepatitis Alliance. “Enough is enough. Governments and global health organisations must ensure all children are vaccinated for hepatitis B and provided with DAAs for hepatitis C, and that all pregnant women are screened.”

Compared to hepatitis C, new hepatitis B infections among children are declining -from approximately 4.7% prevalence in the pre-vaccination era of the early 1980s to 1.3% – due to scaled-up efforts to prevent mother-to-child transmission and global coverage with the three doses of hepatitis B vaccine. Currently, 84% of countries offer hepatitis B vaccinations. However, coverage with the initial birth dose vaccination needed to provide protection to newborns, is still low at 39%.

Cases of hepatitis C in children are, however, likely to continue growing for years to come, given the lack of prevention and control programs for pregnant women living with hepatitis C and women of child bearing age. This is exacerbated by the absence of a public health approach for case definition and management of expectant mothers or children.

“We must act and treat as many children as possible. The economic and social benefit of early hepatitis C treatment in children is substantial,” Professor El-Sayed explains. “This includes avoiding disease progression, removing social stigma and improving activity and school performance, and reducing fatigue. However, the fundamental principle is to avoid transmission by adopting ‘cure as prevention’ at an early age and before high risk behaviours emerge that enable transmission.”

“Children are the future.” Peck concluded. “It’s imperative that we get it right from the beginning and give them the best possible start in life. Without eliminating viral hepatitis amongst children, its elimination will be impossible”.

 

Read also:

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Hepatitis C buyers’ clubs grow worldwide as a way to obtain affordable treatment http://www.eatg.org/news/hepatitis-c-buyers-clubs-grow-worldwide-as-a-way-to-obtain-affordable-treatment/ Tue, 07 Nov 2017 22:50:34 +0000 http://www.eatg.org/?post_type=news&p=6714 Hidden amongst the thousands of Facebook pages given over to holiday snaps and gossip are groups of patients who have hepatitis C, a disease that affects more than 70 million worldwide and kills around 400,000 people a year.

But importantly, these groups of patients from Russia to Australia have got together to help each other import a relatively new class of drug that is able to cure most of the patients who take it.

These buyers’ clubs, as they’re called, are reminiscent of a Hollywood film Dallas Buyers’ Club, where a group establishes to access cheaper HIV drugs.

Dr James Freeman, who was behind the first hepatitis C buyers’ club in Australia and has consulted for others, said in an interview, “There are around a hundred of these around the world and the least one in every [high-income] country.”

The reason that these buyers’ groups have popped up is because many of the hepatitis C drugs on offer in their own countries are extremely expensive. Most can’t access these drugs through their health systems and have now, controversially, taken to importing them from cheaper sources abroad.

The originator companies that first brought these blockbuster drugs to market have offered them for has much as $84,000 for a 12-week course.

Of course, many countries have now negotiated much lower prices with the companies that make the drugs.

The problem is, prices are still not low enough to pay for everybody who has hepatitis C, according to governments, activists and many patients. As a result, only the sickest patients access the drugs, which are heavily rationed in many countries.

And that’s why buyers have now begun to get together to import them from countries where they are much cheaper, said Dr Andrew Hill, a pharmacology expert from the University of Liverpool, United Kingdom. He spoke last week at the World Hepatitis Summit in Sao Paulo, Brazil (1-3 November) and was to present data on the hugely varying cost of a 12-week course of sofosbuvir and daclatasvir, a common combination of such drugs, from $78 in India and $174 in Egypt, and US$6000 in Australia. but it is still $77,000 in the UK, and a staggering $96,404 the USA.

“The negotiated prices of the drugs from originators are still far higher than prices available from generic companies, so there is still a big incentive for people to import the drugs,” he said. “Very few people are aware that this is legal in a range of countries such Australia and the UK.”

Prices are so much lower in India and Egypt because generic companies sell them at close to cost price, according to Hill. They cannot sell their drugs within Europe, for example, because there is a patent.

Speaking from Tasmania, FixHepC’s Freeman said buyers’ groups help individual patients source and buy from drug suppliers in India, Algeria and Egypt, often accessing laboratory tests to confirm their consignments are acceptable, and provide advice on taking the course of medication.

Personal Use

Buyers’ groups are relying on a loophole that allows them to import small amounts of medication for personal use from generics abroad.

These so-called personal importation rules, were designed to allow patients to bring in small amounts of medication even if that medication has not been registered in the country; tourists can visit a country and bring their own medication, or foreign visitors can use their usual medication from home while working and living overseas.

The buyers’ groups are basing their actions on a few elements of the TRIPS agreement (World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights). The most important, Article 60, states that small quantities of goods of a non-commercial nature contained in travellers’ personal luggage or sent in small consignments are permitted.

Freeman said the size of “a small consignment” is not precisely defined within TRIPS but is usually interpreted within many national rules as under 2 kg.

How such consignments are bought and paid for, however, must be managed extremely carefully. “If I bought the medications and sold them to patients that would be illegal. Only licensed pharmacists can sell medications,” he said.

They work something like this: Buyers’ clubs act in the role of the patient’s agent. The buyer is the patient and they are exercising their rights, the seller is in the country of the medication’s origin and is operating within their laws, said Freeman. “Buyers’ clubs link the two – this is legal and no different from any other agent helping a person exercise a transaction,” he added. “So what buyers’ clubs do is de-risk the process, which is, after all a pretty uncommon way of getting a medication.”

Interestingly, several governments from Uruguay to Denmark are relaxing or have relaxed their personal import rules to help patients access drugs from abroad. Switzerland, for example, allowed just one month’s worth of medication to be imported. That has been extended to 3 months.

And at the end of March, Italian Minister of Health Beatrice Lorenzin issued a circular stating that patients and their doctors are allowed to import medicines authorised for sale in other countries for personal use when there is no therapeutic alternative authorised in Italy or when a treatment authorised in Italy is not accessible to patients due to restrictive prescription criteria or because it is too expensive for the patient.

“She did this with only a veiled reference to the high-priced hepatitis C (HCV) medicine sofosbuvir, marketed under the trade name Sovaldi,” Ellen ‘t Hoen at the Global Health Unit Department of Health Sciences, UMCG Groningen, said on her Medicines Law and Policy blog at the time.

But not all countries allow personal imports, however. The US is one example.

That said, individual US states are understood to be discussing strategies to access hepatitis C drugs, some related to personal importation. Louisiana, for example, is mooting the idea of using an old federal law known as 28 USC 1498, which permits the government to directly purchase drugs without regard to their patent status.

“The importation debate is really happening in the US as well, because the states cannot afford these hepatitis C treatments for their people,” said Tahir Amin, a lawyer at I-MAK, which is challenging the hepatitis C drug patents in various countries including the US.

Gilead said it has been working with national healthcare systems toward the goal of enabling unrestricted access to its curative HCV treatments. “Patients in most developed countries have access to our curative HCV medicines via their national healthcare system and do not need to resort to unregulated and uncontrolled buyer’s clubs to receive treatment,” said a spokesperson.

It said it is concerned with patient safety and that the patients cannot be sure what they are receiving through the clubs. “The source and quality of hepatitis C medicines secured through medical tourism and buyers’ clubs are unknown,” the spokesperson said.

Nevertheless, patients worldwide are looking at alternative methods to access the drugs; Irish citizens unable to import drugs are getting on the ferries to buy them in the UK, said FixHepC’s Freeman. Before the import rules changed, Italians were nipping over to Vatican City for cheaper drugs too, said Paolo Corciulo, of Cure-HepC, a company that provides hepatitis C treatment services.

He welcomes the changes, but says there are some drawbacks. For example, quite a bit of paperwork is required beforehand – such as an import request from an Italian doctor. “The main problem is that most of the doctors refuse to fill up the form. They don’t know the generic brand or they just don’t want responsibility,” he said.

Additionally, there are no guidelines on how to deal with reputable dealers, which may expose unsuspecting patients to unscrupulous criminals, he warned. Corciulo has opted instead to take patients to the drugs – 200 have already been on Hep C holidays to India. Here patients can buy the drugs at source and are treated by doctors at reputable Indian hospitals.

But many believe a more wide-reaching strategy is necessary. Countries such as Malaysia recently announced that it will override the patent, and issue a compulsory licence (CL) to import generics medicines so that more of its citizens can be treated.

It is unclear which countries may follow, said the University of Liverpool’s Hill, although Thailand and Brazil have historically issued the most CLs.

“The first step is for these countries to understand how much they could save by going down this path. Few countries realise just how cheaply these drugs can be made, and how much extra they are paying,” he said.

By Tatum Anderson

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For cancer patients with HIV, immunotherapy appears safe http://www.eatg.org/news/for-cancer-patients-with-hiv-immunotherapy-appears-safe/ Tue, 07 Nov 2017 22:45:49 +0000 http://www.eatg.org/?post_type=news&p=6716 Checkpoint inhibitor study suggests new treatment options for patients long excluded from cancer immunotherapy clinical trials.

Read the full publication here.

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Some women with HIV breast-feed in secret http://www.eatg.org/news/some-women-with-hiv-breast-feed-in-secret/ Tue, 07 Nov 2017 22:40:22 +0000 http://www.eatg.org/?post_type=news&p=6715 MILAN — Current guidelines recommend that women with HIV avoid breast-feeding, but some do so without advising their physician and without monitoring for the safety of their baby.

However, when a woman has an undetectable viral load, the risk is minimal, according to some specialists.

“What we need now is a protocol,” Mona Loutfy, MD, from the University of Toronto, said here at the 16th European AIDS Conference.

That just might be on the way. During a lively debate at the conference, Women Against Viruses in Europe (WAVE) — a subgroup of the European AIDS Clinical Society (EACS) — committed to creating formal breast-feeding guidelines.

“This is probably the first group to come together as an organization to put together a recommendation on how to support women,” Dr Loutfy told Medscape Medical News.

The WAVE subgroup plans to work with pediatricians and other clinicians to share effective practices, and to determine whether the field is at the point that it can acknowledge that women are likely breast-feeding without the consent or knowledge of their physicians.

The groundwork for the debate was set when updated clinical guidelines were released by EACS. In addition to updating vaccine recommendations and adding information about comorbidities, the guidelines recommend against breast-feeding. But in case a woman insists on breast-feeding, “we recommend follow-up with increased clinical virological monitoring of both the mother and the infant.”

Even with the strong air of discouragement, this statement is “a breakthrough,” said Dr Loutfy. Three years ago, “no one would have even talked about this.”

What has changed is the thinking about transmission risk in people with suppressed viral loads. In the past few years, some high-profile studies have shown that immediate treatment that results in a suppressed viral load for at least 6 months protects against transmission.

The randomized controlled HPTN 052 trial (N Eng J Med. 2011;365:493-505), the prospective PARTNER cohort (JAMA. 2016;316:171-181), and the Opposites Attract Trial — presented at the International AIDS Society 2017 Conference — all showed that in people with fully suppressed viral loads, there were no transmissions of HIV between partners, whether they were straight or gay, and whether or not they used condoms.

That research, followed by the public information campaign known as Undetectable = Untransmittable, or U=U, has pushed the conversation from strict abstinence or sex only with condoms to the possibility of natural conception between straight serodiscordant couples, as reported by Medscape Medical News.

It has “completely changed the way I practice,” said Dr Loutfy.

She recalled a community meeting that she, HIV physicians, women living with HIV, and other healthcare professionals attended a few years ago. A midwife asked: “Are we going to have this conversation [an insistence on strict bottle-feeding] like we always do? Or are we going to actually acknowledge that women are breast-feeding already and not telling us?”

Dr Loutfy said she was sure that was not true, but woman after woman broke the news to her: they had been breast-feeding. They’d just been doing it in secret, with no support and no viral load monitoring for their infant.

“I was shocked,” she said. “Before, it was just like, no breastfeeding. Now it’s a conversation.”

Switzerland to the Front

Switzerland has been at the front of this conversation for nearly a decade. Before HPTN 052, the Swiss AIDS Federation published a statement saying that if a person with HIV has an undetectable viral load for 6 months, no other sexually transmitted infections, and a monogamous relationship, he or she can have sex without a condom.

That drew counterstatements — insisting on continued condom use — from the World Health Organization and health policy organizations from individual countries.

Now, Switzerland is poised to be one of the first countries in Europe to support breast-feeding by women with undetectable viral loads, albeit accompanied by monthly viral load tests for mothers and weekly tests for infants.

The goal is not universal breast-feeding, said Karoline Aebi-Popp, MD, from the University of Bern in Switzerland. The goal is patient-centered informed consent, where women and their clinicians talk openly about the pros and cons of breast-feeding on an individual basis and discuss the risks and benefits to the mother and child.

“Following that discussion, some may elect to breast-feed,” said Karina Butler O’Connell, MD, from University College Dublin, a pediatrician who advocated for the child in the debate. “But others may change their minds.”

It’s a conversation physicians are already having among themselves, as reported by Medscape Medical News.

“If the woman is undetectable through the whole pregnancy and she insists on breast-feeding, we would support her,” said Dr Aebi-Popp. “The worst thing is if they do it and they don’t tell us.”

Dr Aebi-Popp said she will be collecting data from all the Swiss women who do decide to breast-feed for future research.

Different Ways to Monitor

During the debate, panel members did not agree what monitoring should entail or which clinicians should be involved. Pediatricians, who recently came out against women with HIV breast-feeding in the United States, “are always going to be thinking of the child and say, no.” So physicians must work to build bridges to that specialty, said Dr Aebi-Popp.

Justyna Kowalska, MD, from the Medical University of Warsaw in Poland, said she would never support breast-feeding without the help of a lactation consultant and input from the woman’s obstetrician. A woman might get support from her infectious disease clinician, only to have her obstetrician discourage her from breast-feeding, she told Medscape Medical News.

“It’s a process that requires a lot of people to get on board and understand,” she said.

In addition, physicians grapple with how exactly to monitor viral load.

As mentioned, in Switzerland, the protocol is monthly plasma viral load testing for the mother and weekly testing for the infant. In Germany, the regimen includes monthly breast-milk and plasma viral load testing and an antiretroviral pharmacokinetics test of the infant whenever blood is drawn for routine tests, said Annette Haberl, MD, from Frankfurt University in Germany, who worked with a woman who breast-fed exclusively about 6 years ago. In Canada, Dr Loutfy reported, there is no access to pharmacokinetic tests, but blood tests are conducted.

“Is that good? Is that bad? I don’t know,” said Dr Haberl.

It is a question that will take time to answer with evidence, said Dr Kowalska. The next step will be meeting with individual specialists and women living with HIV to hammer out protocols.

“It won’t come forward in the next year or the year after,” she said, “but it’s a start.”

Dr Loutfy, Dr Aebi-Popp, Dr Haberl, and Dr Kowalska have disclosed no relevant financial relationships.

16th European AIDS Conference. Abstract PS8/2. Presented October 27, 2017.

By Heather Boerner

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Peripheral neuropathy in patients with HIV: association with additional pain disorders http://www.eatg.org/news/peripheral-neuropathy-in-patients-with-hiv-association-with-additional-pain-disorders/ Tue, 07 Nov 2017 22:18:23 +0000 http://www.eatg.org/?post_type=news&p=6713 Patients with a diagnosis of HIV and peripheral neuropathy (HIV-PN) often have ≥1 additional pain disorders, according to an analysis published in Pain Medicine.

Investigators obtained patient data from the Clinical Data Warehouse, using International Classification of Diseases-9/10 diagnostic codes to identify patients with HIV-PN. Of 638 patients with HIV, 68 also had peripheral neuropathy (HIV-PN) and had received primary care and combination antiretroviral therapy, and the remaining patients had not been diagnosed with PN.

Patients with HIV-PN had a greater history of substance use disorder (49% vs 30%; P =.002), which the researchers suggest may be an HIV-PN risk factor. According to the findings, patients with an HIV-PN diagnosis had double the chance of being diagnosed with additional chronic pain syndromes (66% vs 32%; P <.001).

Approximately 36% of patients with HIV-PN had spinal degenerative disorders vs 12% in the population without HIV-PN (P <.001). Following adjustment for potential and clinically relevant confounders, the researchers observed that patients with HIV-PN continued to have significantly more chronic pain disorders (P <.001).

The investigators suggested that the findings may not be generalizable to the entire HIV-PN patient population, since this study examined characteristics of patients living in a low-income, urban community. Also, clinical records were the primary source of patient data, which brings into question the accuracy of HIV-PN and accompanying chronic pain diagnoses as these often depend upon the physician.

Since many patients with HIV-PN appear to have ≥1 chronic pain conditions, physicians are urged to “ask patients with HIV-PN about other types of pain and formulate the pain management plan accordingly.”

By Brandon May

Reference

Navis A, Jiao J, George MC, Simpson D, Robinson-Papp J. Comorbid pain syndromes in HIV-associated peripheral neuropathy. Pain Med [published online August 7, 2017]. doi:10.1093/pm/pnx129

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Australia: Uptake of medications for HIV treatment and prevention changes sexual practices http://www.eatg.org/news/australia-uptake-of-medications-for-hiv-treatment-and-prevention-changes-sexual-practices/ Tue, 07 Nov 2017 21:55:13 +0000 http://www.eatg.org/?post_type=news&p=6711 The latest report by UNSW’s Centre for Social Research in Health shows increasing use of HIV medications to prevent the spread of HIV by gay and bisexual men.

The Annual Report of Trends in Behaviour 2017 released today (November 6) by the Centre for Social Research in Health (CSRH) at UNSW Sydney finds the proportion of non-HIV-positive gay men who reported pre-exposure prophylaxis (PrEP) use in the six months prior to the annual Gay Community Periodic Surveys increased from 2% in 2013 to 5% in 2016.

The increase was mostly seen between 2015 and 2016, suggesting PrEP uptake was boosted by increased availability through the large state-funded PrEP access programs in NSW, Victoria and Queensland in 2016.

PrEP is HIV medication taken by HIV-negative men before sex to prevent HIV. If taken as prescribed, PrEP stops a person from getting HIV.

“Particularly in the last three years, gay and bisexual men are increasingly using PrEP and treatment as prevention (TasP) to manage HIV transmission risk,” said Associate Professor Martin Holt, the project leader of the Gay Community Periodic Surveys at CSRH. “This underscores the growing range of strategies adopted by gay and bisexual men to reduce HIV transmission.”

Also encouraging was that the proportion of HIV-positive gay and bisexual men on antiretroviral treatment (ART) was at a record high for the second year running, which maintains the health of people living with HIV and also contributes significantly to eliminate HIV transmission.

Nationally, 88% of HIV-positive gay men reported being on ART in 2016. ART uptake has increased significantly over the last 10 years, from 57% in 2007. The proportion of HIV-positive gay and bisexual men having an undetectable viral load (which carries no risk of HIV transmission) has also increased by more than 30 percentage points to 88% (the highest on record), from 56% in 2007.

Key findings from the Gay Community Periodic Surveys show that gay and bisexual men are also taking a number of critical steps to negotiate relationships, sex and HIV risk. These measures include:

  • Frequent HIV testing: In 2016, close to one-third of non-HIV-positive gay men had a minimum of three tests within the previous 12 months (one HIV test every four months on average).
  • Comprehensive STI testing: In 2016, 45% of gay and bisexual men reported comprehensive STI testing (a minimum of one blood sample, urine sample, throat swab and rectal swab each) in the previous year.
  • Consistent condom use: For those who had sex with casual male partners in the previous six months, the number reporting consistent condom use during casual encounters in 2016 was just below 40%, down from 44% in 2013.
  • “Serosorting” (seeking partners of the same HIV status): This remains the most commonly used risk reduction strategy by HIV-negative men (45% in 2012, increasing to 52% in 2016). Both HIV-negative and HIV-positive gay men increasingly disclose their HIV status during casual sexual encounters.

“Some gay and bisexual men have gradually moved away from consistent condom use and rely on a range of biomedical and behavioural strategies to reduce HIV transmission,” said Dr Limin Mao, the leading author of this CSRH report.

Continued investment in developing innovative approaches to engage gay and bisexual men in HIV and STI health promotion through various online and mobile platforms should be prioritised.

“This should be carefully monitored and interpreted in the context of increased uptake of testing, treatment and PrEP. We need to better understand these rapid changes and ensure health promotion messages emphasise the effectiveness of a combination prevention approach to suit diverse population needs.”

Dr Mao also said: “Using mobile apps is one of the most efficient ways to find other male sex partners. Continued investment in developing innovative approaches to engage gay and bisexual men in HIV and STI health promotion through various online and mobile platforms should be prioritised.”

CSRH Associate Professor Christy Newman said apart from gay-identified men, there are other priority populations who require better understanding and more attention to address potential disparities in access to new prevention technologies and behavioural risk reduction strategies.

For example, qualitative studies from CSRH offer a range of insights for engaging and serving heterosexual-identified men who sometimes have sex with men, young people from migrant and refugee backgrounds, people who are Medicare ineligible, other people living with HIV (adolescents and children) and heterosexual couples with mixed HIV status.

The Director of CSRH, Professor Carla Treloar, summarised: “Our report highlights the need for further concerted efforts to promote a combination of biomedical and behavioural prevention strategies to drive down rates of HIV or STI infection.

“Equally important is the need to support community-based responses to HIV and STIs, and to substantially reduce stigma, discrimination and other structural barriers associated with diverse populations affected by HIV and STIs.”

Read the full report here.

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Australia: Gonorrhoea and syphilis on the rise, HIV stable, and some good news on hepatitis http://www.eatg.org/news/australia-gonorrhoea-and-syphilis-on-the-rise-hiv-stable-and-some-good-news-on-hepatitis/ Tue, 07 Nov 2017 21:50:48 +0000 http://www.eatg.org/?post_type=news&p=6710 Australia’s annual report card on STIs and blood-borne viruses finds that gonorrhoea has increased by 63% over the past five years.

Gonorrhoea and syphilis diagnoses are increasing in Australia, HIV is stable, and more than 30,000 Australians have been cured of hepatitis C, according to the latest Annual Surveillance Report on HIV, viral hepatitis and sexually transmissible infections (STIs) in Australia, released today (November 6) by the Kirby Institute at UNSW Sydney.

The latest data shows that gonorrhoea has increased by 63% over the past five years, with particular rises among young heterosexual people in major cities.

“Up until recently, gonorrhoea had been uncommon in young heterosexual people living in major cities. Rising rates in this group highlight the need for initiatives to raise awareness among clinicians and young people about the importance of testing,” said Associate Professor Rebecca Guy, head of the Surveillance, Evaluation and Research Program at the Kirby Institute. “With the national strategies for HIV, hepatitis and STIs up for review, reducing STIs in young people will be an important target.”

Among Aboriginal and Torres Strait Islander peoples, chlamydia and gonorrhoea rates were three and seven times higher than in the non-Indigenous population and the gaps were greater in regional and remote areas. Since 2011, there has been a resurgence of infectious syphilis among young Aboriginal and Torres Strait Islander people living in regional and remote areas of Northern Australia.

“Initiatives underway to address the syphilis resurgence include enhanced testing and treatment, and culturally appropriate health promotion campaigns,” said Associate Professor James Ward, head of Infectious Diseases Research, Aboriginal Health Infection and Immunity, South Australian Health and Medical Research Institute. “Comprehensive strategies are needed to reduce STIs in Aboriginal and Torres Strait Islander peoples.”

HIV diagnoses stable for fifth year in a row

The report shows that HIV diagnoses have remained stable in Australia for the past five years, with 1,013 new diagnoses in 2016.

Associate Professor Guy said these results are due to high levels of testing and treatment in Australia. “We’re seeing increased uptake of HIV testing, particularly among gay and bisexual men, who are the population most affected by HIV in Australia,” said Associate Professor Guy. “It is also encouraging that 86% of people diagnosed with HIV were on treatment in 2016.”

However, gaps in testing remain, particularly among heterosexual people, where one in five HIV diagnoses occurs. Nearly half of heterosexual people diagnosed with HIV were diagnosed late, meaning they were likely to have acquired HIV at least four years before diagnosis.

“For HIV to decline nationally, we must focus on a combination of prevention strategies, including enhancing our testing and treatment efforts, making HIV self-testing available and ensuring equitable access to pre-exposure prophylaxis (PrEP) across Australia,” said Associate Professor Guy. PrEP is a treatment which prevents people at risk from acquiring HIV, but is currently only accessible through clinical trials.

“A recent announcement from NSW Health shows early evidence of the impact of this combination of strategies, with a 31% reduction in new HIV diagnoses in gay and bisexual men in the first half of 2017 compared to the previous five years, the lowest count on record,” said Associate Professor Guy.

In contrast, the report indicates that HIV diagnoses among Aboriginal and Torres Strait Islander people have increased by 39% since 2012, with a greater proportion of diagnoses due to injecting drug use and heterosexual sex, compared to non-Indigenous populations.

Associate Professor Ward said that this disparity highlights the need for culturally relevant HIV prevention programs for Aboriginal people. “We need enhanced community education, targeted testing and treatment initiatives – including access to PrEP, and greater access to sterile needle and syringes, and drug dependence treatment for people who inject drugs.”

Some good news on hepatitis, but more work to be done

Between March and December 2016, an estimated 30,434 people have been cured of hepatitis C due to the availability of new direct acting antiviral therapy for hepatitis C.

“The new therapies have been game-changing for hepatitis C in Australia”, said Associate Professor Jason Grebely from the Viral Hepatitis Clinical Research Program at the Kirby Institute.

“Our estimates indicate that the number of people with hepatitis C who have advanced liver disease has fallen for the first time in 10 years. This is excellent news, but to achieve hepatitis C elimination in Australia we must sustain our efforts to ensure all people living with hepatitis C are tested and have access to these cures.”

The report also shows that over the past five years hepatitis B diagnoses have declined by 27% in people aged less than 25 years, reflecting the impact of the infant and adolescent vaccination programs. However, only 63% of the estimated 230,000 people living with chronic hepatitis B in Australia by the end of 2016 were diagnosed. Of those, only 27% were having appropriate clinical monitoring tests for their infection.

“The significant gaps in diagnosis and care highlight the need for better strategies to reach people living with hepatitis B in Australia,” says Associate Professor Ben Cowie, director of the WHO Collaborating Centre for Viral Hepatitis, Doherty Institute.

The decline in hepatitis B diagnoses is also evident in younger Aboriginal and Torres Strait Islander peoples. “It is encouraging to see that immunisation programs for hepatitis B have had a clear benefit in reducing the gap in hepatitis B between Aboriginal and Torres Strait Islander people and the non-Indigenous population,” said Associate Professor Ward. “However, hepatitis B diagnoses in the population over 30 years remain high and a continued focus on testing and vaccination among this population is needed.”

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Metabolic syndrome’s link to liver fibrosis in patients with HIV http://www.eatg.org/news/metabolic-syndromes-link-to-liver-fibrosis-in-patients-with-hiv/ Tue, 07 Nov 2017 21:31:39 +0000 http://www.eatg.org/?post_type=news&p=6709 Although incredible advances in the development and dissemination of antiretroviral therapy (ART) have enabled many individuals with HIV to avoid progressing to AIDS, the efficacy of this therapy means the population may now live long enough to succumb to diseases that often plague the non- HIV–infected population. Chief among these is liver disease, specifically nonalcoholic fatty liver disease (NAFLD), which is characterized by fatty deposits in the liver and can lead to liver fibrosis (stiffness), cirrhosis, or death.

In patients who do not have HIV, the primary driver of NAFLD is metabolic syndrome. According to the National Heart, Lung, and Blood Institute, metabolic syndrome pertains to a cluster of risk factors that predispose a person to heart disease, diabetes, and stroke, and its incidence is rising worldwide. Prominent among these risk factors is obesity concentrated in the abdominal area. Additional risk factors include hypertension, a high fasting blood glucose level, and high triglyceride and low high-density lipoprotein (HDL) cholesterol levels. Now, NAFLD driven by metabolic syndrome is becoming more common in individuals with HIV as well—approximately one-third have NAFLD, according to the authors of a new study on the link between liver fibrosis and metabolic syndrome in individuals living with HIV.1

The study was conducted by a European team that analyzed 405 HIV-monoinfected adults, mostly male, who appeared in a database of patients being followed for treatment at a Paris hospital. The subjects all had been diagnosed with HIV at least 5 years prior to the study, and none had a history of excessive alcohol consumption. Their average age was 53, and 203 had metabolic syndrome. Upon enrollment, each participant had the stiffness of his or her liver measured using transient elastography, a noninvasive method similar to an ultrasound. Blood samples also were taken after a 12-hour fast.

The team found that liver stiffness, along with cirrhosis, was measurably higher in patients who had markers of metabolic syndrome, including low HDL cholesterol and high triglycerides. The higher the patient’s body mass index (BMI), the higher the risk of fibrosis and cirrhosis. Patients with a BMI of at least 30 kg/m2 were especially likely to have fibrosis, as were patients whose blood work suggested insulin resistance. Overall, 25.1% of HIV-monoinfected patients who had metabolic syndrome had significant fibrosis, with 8.4% found to have cirrhosis. Among HIV-monoinfected patients without metabolic syndrome, fewer than 8% had fibrosis. Because fibrosis is a known marker of the severity of chronic liver disease, and because it has a proven association with deaths due to liver disease in individuals with NAFLD who don’t have HIV, these findings have important implications for the HIV community.

Liver disease has long been a concern in individuals living with HIV, especially as they’ve seen their lives extended thanks to ART. “Most of the time, patients with HIV develop liver fibrosis/ cirrhosis in a background of viral hepatitis (hepatitis B virus [HBV] or hepatitis C virus [HCV]) coinfection,” Maud Lemoine, a senior clinical lecturer at Imperial College London and the lead author of the study, told Contagion®. “But in patients without HBV or HCV coinfection, metabolic syndrome [arises] mainly due to obesity inducing fat into the liver, which can progress to inflammation and fibrosis.”

Exactly how and why NAFLD and metabolic syndrome contribute to liver fibrosis in individuals living with HIV is not well understood. Researchers are unsure of the causative biological processes, but they have confirmed that HIV-monoinfected patients with metabolic syndrome experience changes in the levels of proteins emitted by fat tissue as well as higher levels of cells that induce an immune response. “The HIV infection itself is connected to a chronic inflammatory state,” Dr. Lemoine said, but added that scientists do not know whether HIV has a direct impact on the liver. “We analyze patients that are very well suppressed, with no detectable viral load.”

What she and her team do know is that adipose tissue from obesity is the main driver of this condition. “So far, it has been a neglected problem in HIV patients,” she said, noting that there have been many studies examining the role of obesity and metabolic disease in individuals without HIV.

Helping Patients Who Have HIV and Metabolic Syndrome

As it is now recognized that individuals living with HIV are becoming more likely to fall prey to non-AIDS–related maladies as their lifespans increase, the health care community needs to respond accordingly. The causes of obesity in individuals living with HIV, said Dr. Lemoine, include poor diet and lack of exercise—much as they do in the general population. Practitioners who treat individuals living with HIV must be aware of the impact of these factors and help patients create and adhere to strategies to lose weight, get more active, and control their diabetes and hypertension, if those conditions are present.

Alcohol, too, may play a role in the development of liver fibrosis, which physicians and other providers should address. “Excess alcohol consumption is definitely a risk factor for fibrosis, and any discussion about fibrosis must make note of this reversible cause,” Benjamin Young, MD, PhD, senior vice president and chief medical officer of the International Association of Providers of AIDS Care (although not an author of this study), told Contagion®. “Alcohol consumption and dependency should be assessed and addressed, and for those with chronic hepatitis or liver fibrosis, a harm reduction approach should be used to support reduction and cessation.”

According to the National Institute on Drug Abuse, alcohol and drugs are significant problems for individuals living with HIV: one of 3 used drugs or binged on alcohol between 2005 and 2009, and 24% have a problem serious enough that they should be in a substance-abuse treatment program.2

Patients with HIV also need to be screened for hepatitis, traditionally a major driver of liver disease in this population. “Diagnosis, treatment, and—in the case of hepatitis C—cure, of viral hepatitis should be done, and for uninfected individuals, vaccinations to prevent hepatitis A and B should be administered,” Dr. Young said.

What role, if any, does ART play in the development of liver fibrosis? “This has not been clearly demonstrated,” Dr. Lemoine told Contagion®. “Probably [there is] an indirect role…but in our study, the role of ART was not significant.”

A more accurate question might be which drugs used in ART pose the most risk rather than whether ART itself is problematic, as the medical community recognizes that the risks of forgoing ART are greater than the potential risks of administration. “It’s generally appreciated that treating HIV with antiretrovirals reduces the risk of liver fibrosis,” said Dr. Young. “Yet there remains controversy as to whether any particular antiretroviral drug might increase the risk over others.” Older drugs, such as d4T (stavudine) and azidothymidine (AZT), Dr. Lemoine said, seem to be more toxic than newer therapies and might best be avoided. Other studies have shown, for example, that when HIV-infected patients with NAFLD switch from efavirenz to raltegravir, liver steatosis is significantly improved.3

Treatment for NAFLD remains a work in progress. A recent study out of Case Western Reserve University in Cleveland, Ohio, examined whether statins are an appropriate therapy for people living with HIV who have NAFLD, as they have been suggested as a viable NAFLD treatment option for people without HIV.4 Interestingly, the HIV-positive subjects treated with statins experienced an increase in their liver fat scores after 96 weeks compared with the liver fat scores of the HIV-positive placebo takers. Therefore, it would seem that although statins are effective at reducing cardiovascular risks, they cannot be relied upon to treat fatty liver disease—and in fact may be counterproductive.

This study had a few limitations, including its use of a noninvasive method to scan for liver fibrosis and the absence of histological confirmation of this diagnosis with liver biopsies. A small percentage of participants (13%) had invalid transient elastography results that could not be used. The participants were overwhelmingly male, which could have skewed the findings as a previous study found that women living with HIV have significantly lower levels of liver steatosis, or fatty liver, than women without HIV. Also, as this was a cross-sectional study, follow-up is necessary to examine rates of morbidity and mortality in this population. The authors hope the medical community engages in further research to learn more about the exact mechanisms that lead patients with HIV to experience liver fibrosis and how this can be prevented.

By Laurie Saloman

References:

  1. Lemoine M, Lacombe K, Bastard JP, et al. Metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV-monoinfected patients. AIDS. 2017;31(14):1955-1964. doi: 10.1097/QAD.0000000000001587.
  2. National Institute on Drug Abuse. Drug and alcohol use – a significant risk factor for HIV. NIH website. drugabuse.gov/related-topics/trends-statistics/infographics/drug-alcohol-use-significant-risk-factor-hiv. Updated April 2015. Accessed on October 14, 2017.
  3. Macias J, Mancebo M, Merino D, et al. Changes in liver steatosis after switching from efavirenz to raltegravir among human immunodeficiency virus-infected patients with nonalcoholic fatty liver disease. Clin Infect Dis, online edition. DOI: 10.1093/cid/cix467.
  4. El Kamari V, Hileman CO, Mccomsey G. Fatty liver disease in HIV: Predictors and response to statin therapy. Open Forum Infectious Diseases, 2017 Fall; 4(Suppl 1): page S58. DOI: 10.1093/ofid/ofx162.136.
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Italian and U.S. researchers look to the future and explore aging-related issues http://www.eatg.org/news/italian-and-u-s-researchers-look-to-the-future-and-explore-aging-related-issues/ Tue, 07 Nov 2017 21:26:40 +0000 http://www.eatg.org/?post_type=news&p=6708

— Researchers in Italy and the United States predict that by 2035, three-quarters of HIV-positive people in both countries will be over the age of 50.
— 90% of HIV-positive older people will have at least one non-communicable disease such as high blood pressure, elevated lipids, diabetes, or cancer.
— HIV care costs attributable to non-communicable disease are expected to double in Italy and increase 40% in the United States.
— Researchers call for “multidisciplinary patient management” and geriatric medicine training for doctors who care for people living with HIV.

Researchers in Canada and other high-income countries increasingly expect that many people who take combination anti-HIV treatment (ART) every day and achieve and maintain an undetectable viral load and keep up with regular clinic and laboratory visits will achieve a near-normal life span. In light of this tremendous effect of ART on people’s life spans, ministries and departments of health should begin planning for the care that will be required by a growing proportion of aging HIV-positive people. A first step in this process is estimating which diseases and health conditions are occurring in older HIV-positive people now, and then projecting these estimates into the future and calculating their costs.

A team of researchers in Italy and the United States has collected health-related information from about 11,000 HIV-positive people and used this to produce a computer model that could explore some effects of aging. The computer model focused on non-communicable diseases (NCD) and projected health outcomes for aging HIV-positive people in both countries, comparing the years 2015 and 2035.

The computer model predicted that in 2035 the average age of HIV-positive people in Italy will be nearly 60 years and in the U.S. it will be 58 years. Furthermore, it predicted that nearly 90% of HIV-positive older people will have at least one of the following NCDs in 2035:

  • higher-than-normal blood pressure
  • elevated levels of lipids (cholesterol and/or triglycerides) in their blood
  • diabetes
  • cancers unrelated to HIV

To a lesser extent, there will also be increases in heart attacks and strokes.

The researchers therefore predicted that the cost of caring for HIV-positive people will likely rise due to the increased presence of NCDs. The model likely underestimates some of the costs of care, as it takes into account only a handful of NCDs. The research team also made recommendations for interventions to reduce NCDs among older patients and for enhancing the training of doctors and nurses so they can better help look after an aging population.

Study details

The research team adapted a well-validated model previously used in the Netherlands to explore aging among HIV-positive people in that country. The researchers used data from an ongoing study in Italy called ICONA, which is focusing on 7,499 HIV-positive people. Data from the U.S. were obtained from 3,748 HIV-positive people with private insurance coverage from a nationally representative sample.

The researchers’ model focused on the following NCDs:

  • abnormal lipid levels in the blood
  • higher-than-normal blood pressure
  • type 2 diabetes
  • chronic kidney disease
  • cancers unrelated to HIV
  • heart attack
  • stroke

Results—What the future likely holds

By the year 2035, the model predicted the following:

Italy

The average age of HIV-positive patients will be nearly 60 years.

U.S.

The average age of HIV-positive patients will be 58 years.

The proportion of patients who are aged 50 years or older will be as follows:

  • Italy – 76%
  • U.S. – 74%

The proportion of patients who are aged 65 years or older will be as follows:

  • Italy – 29%
  • U.S. – 27%

Focus on non-communicable diseases

According to the researchers, in 2035 “the increasing burden of NCDs will be driven by” the following:

  • higher-than-normal blood pressure
  • abnormal lipid levels in the blood
  • type 2 diabetes
  • cancers unrelated to HIV

The proportions of HIV-positive people who had these conditions in 2015 are as follows:

Higher than normal blood pressure and elevated lipid levels

  • Italy – 60%
  • U.S. – 61%

Type 2 diabetes

  • Italy – 9%
  • U.S. – 12%

Cancers unrelated to HIV

  • Italy – 6%
  • U.S. – 14%

The computer model predicted that the following proportions of HIV-positive people will have NCDs in 2035:

Higher-than-normal blood pressure and elevated lipid levels

  • Italy – 85%
  • U.S. – 84%

Type 2 diabetes

  • Italy – 27%
  • U.S. – 23%

Cancers unrelated to HIV

  • Italy – 16%
  • U.S. – 30%

When researchers assessed trends in heart attacks and strokes, they expected the following proportions of people to have one or more of these conditions in 2035, as follows:

  • Italy – 10%
  • U.S. – 21%

This difference in rates of serious cardiovascular disease between the two countries is, according to the researchers, “driven by the higher age-specific prevalence and incidence of serious cardiovascular disease observed in the U.S. compared to Italy.”

Costs of managing NCDs expected to rise

The researchers estimated the annual costs of care directly related to NCDs and found that the computer model suggested it would increase between 2015 and 2035 in both countries, as follows:

Italy

The researchers estimated that currently 11% of the cost of caring for HIV-positive people arises from treatment of NCDs. By 2035 this figure is expected to rise to almost 23%. The greatest proportion of this increase will be due to the cost of care associated with abnormal lipid levels and chronic kidney disease.

U.S.

The researchers estimated that currently 40% of the total costs of care for HIV-positive people arises from treatment of NCDs. By 2035 this figure is expected to rise to almost 56%.

These findings are supported by studies in the Netherlands, which also suggest that NCDs and in particular cardiovascular disease (and its cost) will increase as HIV-positive people age.

The need to prevent NCDs

According to the researchers, “The aging of the HIV-positive populations in Italy and the U.S. will have major implications for HIV care. Our forecasts suggest that three-quarters of HIV-positive patients on ART will be over 50 years in both countries by 2035, resulting in an increased NCD burden in this population.” Recall that the main drivers of this burden of NCDs will be as follows:

  • higher-than-normal levels of blood pressure
  • abnormal lipid levels in the blood
  • type 2 diabetes
  • cancers unrelated to HIV

Furthermore, the researchers said:

“These shifts [toward NCDs] will have considerable implications for direct HIV care costs, with average care costs attributable to NCD treatment expected to double in Italy and increase by 40% in the U.S. Evidence-based approaches on effective prevention interventions and treatment protocols will be vital to mitigate this growing burden.”

A change in health management

In high-income countries, as patients initiate ART earlier in the course of HIV disease, care provided by doctors, for the most part, continues to shift from preventing the life-threatening infections that are the hallmark of AIDS to what the research team called “the long-term prevention, screening and treatment of NCDs.” The researchers underscored that as this shift continues the following aspects of care and treatment will need particular attention:

  • choice of the best ART regimen
  • management of interactions between ART and medicines used to prevent and treat NCDs
  • adherence not just to ART but also to NCD medicines

As patients age, the researchers call for “multidisciplinary patient management” focusing on the following elements of optimal health:

  • principles of geriatric medicine
  • personalized treatment protocols
  • interventions with patients to help prevent or minimize the effects of NCDs, such as guidance on risk factors that can be modified (quitting smoking, dietary changes, exercise and so on)

To help effect these changes, the researchers call for training in geriatric medicine to become available for healthcare providers, particularly family medicine specialists.

The publication of the model’s results should stimulate other countries and regions to conduct their own assessments of the trajectories of people with HIV as they age and which NCDs need to be prevented and treated.

Bear in mind

There are several issues that may affect the present model’s accuracy:

  • Researchers focused on a handful of NCDs. Future computer models could add other NCDs such as asthma, chronic obstructive pulmonary disease, obesity and so on.
  • Researchers did not take into account cognitive impairment, which can occur because of HIV and also because of aging.
  • The U.S. data came from patients who had private health insurance coverage that provided what the researchers called “the best access to health care.” Such patients might be healthier than patients who rely on public health programs or those without health insurance.

These and other reasons suggest that the computer model is likely to have underestimated future NCDs and associated healthcare costs.

By Sean R. Hosein

REFERENCES:

  1. Smit M, Cassidy R, Cozzi-Lepri A, et al. Projections of non-communicable disease and health care costs among HIV-positive persons in Italy and the U.S.A.: A modelling study. PLoS One. 2017 Oct 23;12(10):e0186638.
  2. Smit M, van Zoest RA, Nichols BE, et al. Cardiovascular disease prevention policy in HIV: recommendations from a modelling study. Clinical Infectious Diseases. 2017; in press.
  3. Smit M, Brinkman K, Geerlings S, et al. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infectious Diseases. 2015 Jul;15(7):810-8.
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Adolescents at risk for HIV should be offered PrEP http://www.eatg.org/news/adolescents-at-risk-for-hiv-should-be-offered-prep/ Tue, 07 Nov 2017 21:04:07 +0000 http://www.eatg.org/?post_type=news&p=6705 AIDS is the second leading cause of death among adolescents globally; approximately 1.8 million individuals aged 10 to 19 years were reported to have HIV in 2015.1 In that age bracket, it was estimated that a new HIV infection occurred every 2 minutes. According to 2014 statistics for the United States, 80% of new cases among individuals aged 13 to 24 years affected young men who have sex with men (YMSM).2

Although tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) received approval from the US Food and Drug Administration in 2012 for HIV preexposure prophylaxis (PrEP), the efficacy trials only included adults, and therefore TDF/FTC was not approved for use in minors.3-5 “Thus, a critical gap in approved prevention products exists for adolescents, a population that is highly vulnerable to HIV worldwide,” wrote the authors of a new study published in JAMA Pediatrics.6

To that end, the authors conducted the Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) to examine the safety, tolerability, and adherence to PrEP among healthy YMSM aged 15 to 17 years, as well as patterns of adherence to the daily regimen and risky sexual behavior.

The sample included 78 individuals with a mean age of 16.5 years (SD, 0.73 years), representing a variety of races and ethnicities, who were recruited from clinics in 6 US cities. Participants had negative test results for HIV but a high risk for infection. For inclusion, they were required to participate in a behavioral intervention, in addition to accepting a 48-week PrEP intervention.

The findings show 23 sexually transmitted infections diagnosed in 12 participants during the study period, as well as 3 new cases of HIV (HIV seroconversion rate, 6.4 [95% CI, 1.3-18.7] per 100 person-years). Tenofovir diphosphate levels indicating a high degree of protection against HIV (>700 fmol/punch) were noted in 54%, 47%, 49%, 28%, 17%, and 22% of participants at weeks 4, 8, 12, 24, 36, and 48, respectively. These results “strongly support the need for an adolescent PrEP indication for TDF/FTC,” the authors concluded. “The waning adherence, especially with quarterly visits, demonstrates that more time, attention, and resources may need to be allocated to adolescents who are seeking prevention services.”

To further explore this topic, Infectious Disease Advisor checked in with 2 experts: study coauthor Bill G. Kapogiannis, MD, program director of the Adolescent Medicine Trials Network for HIV/AIDS Interventions of the Eunice Kennedy Shriver National Institutes of Child Health and Human Development; and Helen C. Koenig, MD, MPH, associate professor of clinical medicine in the Division of Infectious Diseases at the Perelman School of Medicine at the University of Pennsylvania, and director of the PrEP program at Philadelphia FIGHT.

Disclaimer: The comments and views below are of the author and do not necessarily represent the views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Infectious Disease Advisor: Dr Kapogiannis, regarding the findings from your most recent paper, what are the main takeaways for our clinical audience?

Dr Kapogiannis: In this first safety and demonstration licensure-bridging study of PrEP to prevent HIV in adolescent minors who are at risk for infection, PrEP was safe and well tolerated. Adherence to PrEP as measured by objective drug levels started off high but decreased over time, and this decline seemed to be associated with decreasing study visit frequency (monthly to quarterly). The 3 incident HIV infections that occurred among participants with very low to undetectable PrEP levels are a stark reminder that the drug cannot work if it isn’t taken. Adolescents at risk for HIV can safely use and should be offered PrEP to reduce their risk of becoming infected, but may need additional support compared with adults, such as more frequent in-person clinic contact, cell phone reminders, and peer support group, to ensure they maintain high adherence.

Infectious Disease Advisor: What are some of the top points of debate regarding PrEP for adolescents?

Dr Kapogiannis: The main point that seems to surface is whether adolescents who are at risk for HIV infection can maintain the high levels of adherence needed for PrEP to be effective. Another, albeit less common, point that comes up is whether prescriptions of PrEP to at-risk adolescents will lead to more risky behaviors or a behavioral phenomenon that is termed disinhibition, which has not been seen in studies so far. Finally, the poor access and uptake in the very communities of young people in the United States who are at greatest risk of becoming infected by HIV is concerning and needs to be addressed.

Dr Koenig: We know that the group in which the HIV incidence is rising the fastest is youth and young adults aged 13 to 24 years, and that among this group the hardest hit subpopulation is young MSM of color and young transwomen of color. Top points for debate are the following:

  • How to get pediatricians to talk with youth about PrEP in a systematic and nonjudgmental way; that is, at a routine visit, to talk about exercise, diet, smoking, routine vaccines, family planning, and HIV prevention options including PrEP with all patients, not just those deemed “at risk”
  • How to get PrEP offered and discussed in schools
  • The difficulty of reaching out to young sexually active women: In my experience, when we have started a young at-risk woman on PrEP and she has been enthusiastic, she then goes home and talks with her friends and none of them have heard about or been offered PrEP, and so the patient stops PrEP, given the absence of peer knowledge or support of PrEP in the young female adult community
  • The need for parental consent
  • The fact that TDF/FTC is not approved for PrEP for those younger than 18 years
  • Concern about TDF affecting bone mineral density in youth who are still growing and laying down bone matrix
  • Medication coverage for minors who do not want to use their parents’ insurance

Infectious Disease Advisor: Is parental permission necessary for PrEP in minors?

Dr Kapogiannis: The answer here is a bit complex, with some important caveats, and in the United States, it is guided at the local/jurisdictional or state level. First, the requirement for parental permission may make it very difficult to nearly impossible for adolescents who are at risk for HIV infection to access PrEP because they may not be willing to disclose required information about their risk behaviors to their parents. Also, the parent-child relationships may not be optimal, or the parent may be absent: Many of the teenagers at risk are at higher risk because they lack a stable, supportive home and family environment. In such situations, there are precedents for foregoing parental consent in adolescents when it comes to protecting their health and safety. One of those sample precedents includes medical care for the diagnosis or treatment of sexually transmitted infections (STIs).

All US jurisdictions expressly allow some minors to consent to medical care for the diagnosis or treatment of STIs. These laws are intended to encourage adolescents to seek treatment for reproductive health concerns through protecting their right to privacy in reproductive health decisions. Because HIV is mainly a STI, adolescents should be allowed to consent for HIV treatment regardless of whether state law specifically mentions HIV. However, state laws may not explicitly address an adolescent’s right to consent to medical care for the prevention of STIs. One could argue, and I would, that the extension of treatment statutes to STI prevention would be consistent with the intent of such state laws to protect the health of adolescents.

Finally, I always encourage adolescents to involve their parents in making healthcare decisions whenever possible, and they feel safe and supported in doing so.

Dr Koenig: “Is” and “should” are 2 different questions, as every state has different policies on STI/HIV prevention and treatment, and different institutions within the same state vary on what they deem medico-legally acceptable. At FIGHT, as in many other places, we believe that PrEP is just like any other state-sanctioned STI prevention intervention that can be legally offered to minors without parental consent. As a parent, I believe consent can and should be obtained wherever possible, as parental involvement can be a wonderful thing that facilitates adherence and engagement in care. However, sometimes obtaining parental consent endangers a young person’s safety; for example, if parents are not aware the patient is MSM and starting TDF/FTC “outs” them in some way, jeopardizing the emotional or physical well-being of an adolescent or financial support or housing for a young adult.

Youth not wanting parents to know they are sexually active for a variety of reasons has been a barrier with the approval of the Gardasil vaccines, home pregnancy testing kits, and so on. In these cases, PrEP can and should be offered without parental consent, again in keeping with the laws of each particular state. At FIGHT, we have codified policy allowing us to prescribe PrEP to minors. However, at the Children’s Hospital of Philadelphia, PrEP cannot be prescribed to minors, given the academic center’s legal concerns, just to give you a sense of some of the variation in practice.

Infectious Disease Advisor: Should PrEP be offered on a wider scale as part of sex education?

Dr Kapogiannis: We don’t know yet whether a “school-based clinic” alternative to the more traditional clinic-based model works better at improving uptake and adherence to PrEP for adolescents at risk for HIV infection, so more research is needed to inform whether this approach is feasible and appropriate.

Dr Koenig: A resounding “Yes,” for all of the above reasons and more. It works! Also, the question, “Why not?” must be asked. Why not share a widely available, acceptable, safe, and effective technology that can prevent a lifelong life-threatening disease, a technology that also serves to engage young people in healthy ongoing care with a healthcare provider, where they can be offered continual risk reduction prevention interventions such as STI testing, family planning assistance, condoms, flu shots, nutrition guidance, smoking cessation support, and general wellness interventions? PrEP IS primary care for youth.

By Tori Rodriguez

References

  1. UNAIDS. Global AIDS update. http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-2016. Updated May 31, 2016. Accessed October 17, 2017.
  2. Centers for Disease Control and Prevention. HIV among youth fact sheet. https://www.cdc.gov/hiv/pdf/group/age/youth/cdc-hiv-youth.pdf. Updated April 2017. Accessed October 17, 2017.
  3. Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587-2599.
  4. Baeten JM, Donnell D, Ndase P, et al; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399-410.
  5. Thigpen MC, Kebaabetswe PM, Paxton LA, et al; TDF2 Study Group. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423-34.
  6. Hosek SG, Landovitz RJ, Kapogiannis B, et al. Safety and feasibility of antiretroviral preexposure prophylaxis for adolescent men who have sex with men aged 15 to 17 years in the United States [published online September 5, 2017]JAMA Pediatr. doi:10.1001/jamapediatrics.2017.2007
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Should dolutegravir be used as maintenance therapy for HIV? http://www.eatg.org/news/should-dolutegravir-be-used-as-maintenance-therapy-for-hiv/ Tue, 07 Nov 2017 19:57:48 +0000 http://www.eatg.org/?post_type=news&p=6704 For patients who take antiretroviral drugs after being diagnosed with HIV, getting viral levels under control is the first step. The next step is keeping viral levels suppressed indefinitely via maintenance therapy. Figuring out which medications provide the best chance of achieving ongoing viral suppression while causing the fewest side effects is, therefore, of paramount importance.

Based on the results of an earlier small retrospective observational study, which suggested that dolutegravir’s high barrier to drug resistance—along with its once-a-day dosing schedule and lack of impact on blood lipid levels—might make it a good choice for a maintenance monotherapy, researchers from the Netherlands conducted their own trial to confirm whether this was true.

They recruited 104 subjects living with HIV who had already been treated with antiretroviral therapy (ART); all were virologically-suppressed, with RNA counts of less than 50 copies per mL and CD4 counts that had never dropped below 200. Fifty-one patients were assigned to immediately switch from combination ART to dolutegravir, and 53 patients switched to dolutegravir after 24 weeks of continuing on their regimen of combination ART. One goal of the study was to see how many patients had RNA viral loads of less than 200 copies per mL at the end of 24 weeks, which would signify adequate viral suppression. The patients were assessed again at 48 weeks.

During the study, one of the subjects who had immediately switched to dolutegravir had to drop out due to sleep disturbances. Of the subjects who continued taking combination ART for 24 weeks, six left the study before the 24 weeks were up for various reasons, including noncompliance and physicians’ recommendations. At 24 weeks, the 47 remaining subjects switched from combination ART to dolutegravir, with one subject subsequently dropping out because of sleep disturbances and one leaving the trial due to headaches.

The researchers found that at 24 weeks, dolutegravir was not inferior to combination ART when it came to viral suppression. Only one patient out of the 50 subjects who switched to dolutegravir immediately had RNA viral loads of 200 copies per mL or higher. None of the patients who delayed switching to dolutegravir had RNA viral loads at that level. However, the scientists concluded that they cannot recommend dolutegravir as a maintenance drug.

“Despite these promising results, virological failure was observed in seven additional patients after week 24, which led to virological suppression in 92% of patients at the time of study discontinuation,” the authors wrote in the study, which was published in The Lancet. “This result was statistically inferior to the 98% suppression rate observed in patients in the concurrent control group.”

The authors noted that all 8 patients who failed to achieve viral suppression on dolutegravir did achieve it once they returned to a regimen of combination ART, although that alone did not mean dolutegravir was an inappropriate choice for maintenance therapy. Upon sequencing the virus in six study subjects, the team discovered that mutations associated with medication resistance had arisen.

“Given the detection of resistance mutations in the integrase gene of more than two patients on dolutegravir monotherapy in our study, with the potential for cross resistance to other available and future integrase inhibitors, one of the stopping rules was met and the study was terminated,” they wrote.

The researchers’ conclusion? Dolutegravir is not an appropriate choice for maintenance monotherapy, a sentiment shared by Janine M. Trevillyan, MBBS, and Jennifer F. Hoy, MBBS, FRACP, Australian scientists who provided additional commentary in The Lancet. “The focus must now switch to the more promising dual-therapy options (such as dolutegravir and lamivudine or rilpivirine), or which large, randomised trials are underway,” they wrote.

By Laurie Saloman

 

Read also:

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CDC contraception recommendations updated for women at risk for HIV http://www.eatg.org/news/cdc-contraception-recommendations-updated-for-women-at-risk-for-hiv/ Tue, 07 Nov 2017 19:43:59 +0000 http://www.eatg.org/?post_type=news&p=6703 In a recent update published in the Morbidity and Mortality Weekly Report, the Centers for Disease Control and Prevention (CDC) revised its US Medical Eligibility Criteria for Contraceptive Use (US MEC) categorization for depot medroxyprogesterone acetate (DMPA) injection in women at high risk for HIV infection from US MEC category 1 to US MEC category 2.

The US MEC update was based on the recent publication of studies evaluating the impact of hormonal contraception on the risk of HIV acquisition and the recent World Health Organization (WHO) guidance published on the same matter. The review committee was comprised of 8 participants who are experts on family planning and HIV infection, seven of whom were from outside the CDC.1

After reviewing the available evidence and information regarding contraception and risk of acquiring HIV, the US MEC recommendation for DMPA injections in women at high risk for HIV infection was revised from category 1 (no restrictions) to category 2 (benefits outweigh theoretical or proven risks). The change was in accordance with the recent WHO guidelines.

Implants, progestin-only pills, and combined hormonal contraceptive remained category 1 in the US MEC.

The change in the US MEC stemmed in part from evidence in a systematic review that indicated that women who used DPMA injections were at an increased risk for HIV acquisition (adjusted hazard ratio 1.4, 94% CI 1.2-1.6).2 The results across studies were inconsistent, and studies may have had methodologic flaws, according to the authors of the report.1

The report further stated that the sociodemographic factors that overlap with DMPA use and increased risk for HIV infection are the same globally and in the United States.1

In an interview with Infectious Disease Advisor, Naomi Tepper, MD, MPH, of the Division of Reproductive Health at the CDC, noted that based on the category 2 recommendation, “women should not be denied the use of DMPA because of concerns about a possible increased risk, but should be counseled about the risks and about how to reduce their risk of acquiring HIV.”

By Jessica Martin

Reference

Tepper NK, Krashin JW, Curtis KM, Cox S, Whiteman MK. Update to CDC’s U.S. medical eligibility criteria for contraceptive use, 2016: revised recommendations for the use of hormonal contraception among women at high risk for HIV infection. MMWR Morb Mortal Wkly Rep. 2017;66:990-994.

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Treating HCV in HIV-coinfection: still a therapeutic dilemma? http://www.eatg.org/news/treating-hcv-in-hiv-coinfection-still-a-therapeutic-dilemma/ Tue, 07 Nov 2017 19:36:51 +0000 http://www.eatg.org/?post_type=news&p=6702 All patients with HIV infection should be screened at least once for HCV. In patients with continued risk factors, such as injecting drug use or men who have sex with men, HCV screening should be repeated. Consequently, there are several treatment sensitivities that need to be taken into account when treating coinfected individuals.

Read the full publication here.

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CATIE: October/November 2017 issue of TreatmentUpdate now online http://www.eatg.org/news/catie-octobernovember-2017-issue-of-treatmentupdate-now-online/ Tue, 07 Nov 2017 15:35:03 +0000 http://www.eatg.org/?post_type=news&p=6707 TreatmentUpdate is CATIE’s flagship digest on cutting-edge developments in HIV and hepatitis C research and treatment.

TreatmentUpdate 222: Anti-HIV agents, October/November 2017 issue is available at:

http://www.catie.ca/en/treatmentupdate/treatmentupdate-222

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News from EACS 2017 http://www.eatg.org/news/news-from-eacs-2017/ Tue, 07 Nov 2017 15:33:10 +0000 http://www.eatg.org/?post_type=news&p=6697 The 16th European AIDS Conference (EACS 2017) took place on 25-27 October 2017 in Milan, Italy.

 

HIV i-Base reports:

 

NATAP reports:

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UNAIDS launches 2017 World AIDS Day campaign—My Health, My Right http://www.eatg.org/news/unaids-launches-2017-world-aids-day-campaign-my-health-my-right/ Mon, 06 Nov 2017 22:55:20 +0000 http://www.eatg.org/?post_type=news&p=6693

GENEVA, 6 November 2017—In the lead up to World AIDS Day on 1 December, UNAIDS has launched this year’s World AIDS Day campaign. The campaign, “My Health, My Right” focuses on the right to health and explores the challenges people around the world face in exercising their rights.

“All people, regardless of their age, gender, where they live or who they love has the right to health,” said Michel Sidibé, Executive Director of UNAIDS. “No matter what their health needs are everyone requires health solutions that are available and accessible, free from discrimination and of good quality.”

The right to health is enshrined in the 1966 International Covenant on Economic, Social and Cultural rights as the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. This includes the right of everyone to the prevention and treatment of ill health, to make decisions about one’s own health and to be treated with respect and dignity.

The campaign reminds people that the right to health is much more than access to quality health services and medicines, but that it also depends on a range of important assurances including, adequate sanitation and housing, healthy working conditions, a clean environment and access to justice among others.

If a person’s right to health is compromised they are often unable to effectively prevent disease and ill health, including HIV, or to gain access to treatment and care. The most marginalized in society, including sex workers, people who inject drugs, men who have sex with men, people in prisons and migrants, are often the least able to access their right to health, they are also the most vulnerable to HIV.

Most of the Sustainable Development Goals are linked in some way to health. To achieve the Sustainable Development Goals, including ending the AIDS epidemic as a public health threat by 2030, will depend heavily on ensuring the right to health for all.

“My Health, My Right” encourages people share their views and concerns around ensuring their own right to health and to create a movement, highlighting the importance of erasing health inequalities. Campaign materials include suggested tweets, downloadable posters and postcards and an information brochure which includes key messages about the right to health.

For more information go to: www.unaids.org

UNAIDS

The Joint United Nations Programme on HIV/AIDS (UNAIDS) leads and inspires the world to achieve its shared vision of zero new HIV infections, zero discrimination and zero AIDS-related deaths. UNAIDS unites the efforts of 11 UN organizations—UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, UN Women, ILO, UNESCO, WHO and the World Bank—and works closely with global and national partners towards ending the AIDS epidemic by 2030 as part of the Sustainable Development Goals. Learn more at unaids.org and connect with us on Facebook, Twitter, Instagram and YouTube.

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UNAIDS: Living with HIV but dying from TB http://www.eatg.org/news/living-with-hiv-but-dying-from-tb/ Mon, 06 Nov 2017 22:50:15 +0000 http://www.eatg.org/?post_type=news&p=6692

Global progress to End TB not fast enough to reach global TB and HIV targets

03 November 2017 – Tuberculosis (TB) retains its undesirable status as the leading infectious cause of death globally. According to the latest WHO Global Tuberculosis Report 2017 launched this week, global progress in reducing new tuberculosis (TB) cases and deaths is insufficient to meet the global targets for TB and HIV, despite most deaths being preventable with early diagnosis and appropriate treatment of tuberculosis and HIV.

As part of global efforts to advance the response to TB is now being pushed higher up the global development agenda with hundreds of global leaders attending the first WHO Global Ministerial Conference on Ending TB in Moscow from 14-17 November and a dedicated United Nations General Assembly High-Level Meeting on TB in 2018.

“We have an unprecedented opportunity to shine the political spotlight on the inequalities that drive the epidemics of TB and HIV,” said Michel Sidibé, UNAIDS Executive Director, “The return on investment in TB and HIV is more than just dollars, it’s in voices heard, rights protected and lives saved.”

In 2016, the risk of developing TB disease among the 37 million people living with HIV was around 21 times higher than the risk in the rest of the world population. There were more than one million TB cases among people living with HIV—10% of all global TB cases in 2016. People living with HIV are much more likely to die from TB disease than HIV-negative people, and one in five (22%) TB deaths occurs among people living with HIV. In 2016, there were 374 000 TB deaths among people living with HIV, which represents almost 40% of all AIDS-related deaths.

TB disease and deaths can be avoided with TB preventive therapy but most people living with HIV who can benefit are not receiving it. In 2016, fewer than 1 million people newly enrolled in HIV care were started on TB preventive treatment. South Africa accounted for the largest share of the total (41%), followed by Mozambique, Zimbabwe and Malawi.

The global burden of drug-resistant tuberculosis continues to rise with an estimated 600,000 cases requiring treatment but only one in five were enrolled on treatment in 2016.

Global TB incidence is only falling at about 2% per year and 16% of TB cases die from the disease; by 2020, these figures need to improve to 4–5% per year and 10%, respectively, to reach the first (2020) milestones of the WHO End TB Strategy. Major gaps remain in global funding for TB prevention and treatment (US$2.3 billion) and TB research into new drugs, vaccines, and diagnostics (US$1.2 billion) for 2017.

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HCV: Miracle cure costs less than a budget airline flight http://www.eatg.org/news/hcv-miracle-cure-costs-less-than-a-budget-airline-flight/ Mon, 06 Nov 2017 22:45:42 +0000 http://www.eatg.org/?post_type=news&p=6696 The revolution in generic drugs means that a 12-week course of drugs to cure hepatitis C can be manufactured for just US$50 – as low as the cost of a plane ticket on many low-cost airlines. Furthermore, new data shows that these generic copies are just as effective as the branded medicines. Yet restrictions and patent issues around the world mean that hardly any patients can access the drugs at these low costs, say experts speaking at the World Hepatitis Summit in Sao Paulo, Brazil (1-3 November).

“As there are around 70 million people infected with hepatitis C worldwide, the basic cost of the drugs to treat everyone infected globally, at $50 each, would be around US $3.5 billion,” explains Dr Andrew Hill, a pharmacology expert from the University of Liverpool, UK. This represents less than a fraction of 1% of the global health budget of some US$ 8 trillion. “Much more must be done to enable all countries — but especially developing countries — to produce or buy drugs for these lower prices. Without significant changes to pricing structures, the battle against the global hepatitis C epidemic simply can’t be won.”

In his presentation, Dr Hill will present data on the hugely varying cost of a 12-week course of sofosbuvir and daclatasvir, a common combination of the new directly acting antiviral drugs (DAAs) that have revolutionised hepatitis C treatment by providing rapid cure with few or no side effects. The list price for this combination of drugs ranges from close to cost price in India ($78) and Egypt ($174) to $6,000 in Australia, $77,000 in the UK, and a staggering $96,404 the USA. Yet the basic cost of the active ingredients, including formulation and packaging costs and even allowing a small profit margin for the generic companies brings the basic cost down to under $50 per course.

In high-income countries, most of which have treatment restrictions allowing only those with advanced disease to be treated first, some infected patients have resorted to buying generic drugs from international buyers’ clubs (who buy in bulk from developing countries) or directly from countries where they are manufactured. For example, in the UK, those not wanting to wait for advanced disease to be treated have been able to legally purchase a 12-week generic course for prices ranging from US $1000 to $1200. Research studies on these patients show that cure rates are as high as for the branded medicines, ranging from 90% to 95%.

An analysis presented at the summit on the efficacy of generic DAAs looked at 1160 patients who have imported DAAs for personal use into 88 countries on 5 continents. Data from these patients show that cure rates are well over 90%, the same as for the branded products, but at a fraction of the cost.

“In 2016, for every person cured of hepatitis C globally (1.76 million), another person was newly infected (1.5 million). We simply cannot eliminate this epidemic unless we treat more people. And we can only do this if the prices of the drugs come down,” explains Dr Hill.

He adds that the manufacturers of DAAs must do more to provide voluntary licences in countries that do not currently have them for generic companies to produce cheaper (but just as effective) generic DAAs. This is what has happened in Egypt, which had nearly 7 million people to treat, but now have fewer than 5 million. However, more than half of those people infected globally live in countries with no voluntary licence to allow generic production. “For example, China and Russia, two countries with very large hepatitis C epidemics, have no voluntary licence in place to produce cheap generic drugs,” explains Dr Hill.

However, Dr Hill makes clear that any efforts to reduce drug prices and enable mass generic DAA production worldwide will be futile unless countries also step up their efforts to find and diagnose their infected populations. “We cannot treat people if we do not know who they are,” explains Dr Hill. “Countries must massively step up their screening efforts, or they will simply run out of people to treat – a diagnostic ‘burn-out’. The proportion of patients with hepatitis C who know they have it ranges from 44% in high-income countries to just 9% in low-income countries.”

He concludes that lessons can and should be learned from the HIV epidemic to successfully end the hepatitis C epidemic worldwide. “It has taken the world 15 years to get 19 million people globally on antiretroviral treatments for HIV,” he says. “We already have the drugs necessary to eliminate hepatitis C. Let’s learn from the past, and repeat the medical success story of global HIV treatment.”

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MPP and USAID sign Memorandum of Understanding http://www.eatg.org/news/mpp-and-usaid-sign-memorandum-of-understanding/ Mon, 06 Nov 2017 22:40:25 +0000 http://www.eatg.org/?post_type=news&p=6695 Geneva, 02 November 2017 — The Medicines Patent Pool and the United States Agency for International Development (USAID) signed a Memorandum of Understanding (MoU) to accelerate the introduction of quality, affordable new medicines for diseases that disproportionately affect developing countries.

The two parties currently collaborate as part of the OPTIMIZE consortium, supported by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and dedicated to rapidly improving treatment outcomes for people living with HIV in low- and middle-income countries.

The USAID-MPP partnership aims to facilitate the development and early introduction of better-formulated antiretrovirals, including those prioritized by OPTIMIZE. The MPP and USAID will coordinate efforts on market intelligence, supplier engagement and technical support in key PEPFAR countries. The MoU also envisions the two parties working together in other areas to address access to medicines issues for HIV as well as for other select diseases in the future.

The MPP’s HIV, hepatitis C and tuberculosis activities are fully funded by Unitaid. USAID and Unitaid are collaborating to accelerate access to optimal antiretroviral regimens for people living with HIV. This collaboration supports a number of projects to develop and introduce better, more affordable treatments in low- and middle-income countries. The Project Advisory Committee (PAC) established by Unitaid and USAID is currently convening in Washington D.C. The committee brings together partners to find new ways to optimise treatments for HIV.

Access the MoU

Learn more about OPTIMIZE

Access the press release in Spanish

About the Medicines Patent Pool

The Medicines Patent Pool is a United Nations-backed public health organisation working to increase access to HIV, hepatitis C and tuberculosis treatments in low- and middle-income countries. Through its innovative business model, the MPP partners with industry, civil society, international organisations, patient groups and other stakeholders to prioritise, forecast and license needed medicines and pool intellectual property to encourage generic manufacture and the development of new formulations. To date, the MPP has signed agreements with nine patent holders for thirteen HIV antiretrovirals, one HIV technology platform, two hepatitis C direct-acting antivirals and a tuberculosis treatment. The MPP was founded and is funded by Unitaid.

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Starting ART immediately after HIV diagnosis cuts mortality risk by two-thirds for people with high CD4 cell counts http://www.eatg.org/news/starting-art-immediately-after-hiv-diagnosis-cuts-mortality-risk-by-two-thirds-for-people-with-high-cd4-cell-counts/ Mon, 06 Nov 2017 22:15:47 +0000 http://www.eatg.org/?post_type=news&p=6691

People with a high CD4 cell count who start antiretroviral therapy (ART) immediately after diagnosis with HIV cut their 12-month mortality risk by two-thirds, according to research conducted in China and published in Clinical Infectious Diseases.

The retrospective study involved over 35,000 people who were newly diagnosed with HIV between 2012 and 2014. All had a CD4 cell count above 500 cells/mm3. Over 12 months of follow-up, individuals who started antiretrovirals within 30 days of their diagnosis had a 63% reduction in their mortality risk compared to people who remained antiretroviral-naïve. Delayed treatment (initiation after 30 days of diagnosis) also reduced mortality, but only by 26%.

“Our results demonstrate that PLWH [people living with HIV] with a CD4 cell count > 500 cells/mm3 who initiated ART within 30 days of diagnosis…experienced a 63% decrease in mortality,” write the investigators. “Additional risk factors for mortality in this study were older age, being male, having lesser education, and becoming infected via injection drug use or heterosexual contact.”

Since 2015, the World Health Organization has recommended that all people with HIV should take antiretroviral therapy, regardless of CD4 cell count. This is because research has proved that treatment, even at high CD4 cell counts, reduces the risk of illness and death. Moreover, people taking treatment who have an undetectable viral load have an effectively zero risk of transmitting HIV to their sexual partners.

Investigators in China wanted to see if immediate ART cut the mortality risk for people with a high CD4 cell count (above 500 cells/mm3) at the time of their diagnosis. They therefore designed a retrospective study involving approximately 35,500 adults newly diagnosed with HIV between 2012 and 2014. All had a CD4 cell count above 500 cells/mm3 and were followed for 12 months after their diagnosis. Study participants were divided into three groups according to their use of HIV therapy:

  • Immediate ART: initiation within 30 days of diagnosis.
  • Deferred ART: initiation more than 30 days after diagnosis.
  • No ART: no HIV treatment.

The researchers hypothesised that immediate ART would be associated with a reduced risk of mortality.

The participants had a median age of 32 years, 75% were male, 64% had a primary education or less, 39% were married, 60% acquired HIV through heterosexual contact. Median baseline CD4 cell count was 616 cells/mm3.

ART was started within 30 days of diagnosis by 5% of the cohort. A further 16% initiated therapy more than 30 days after diagnosis and the remaining people remained ART naïve.

A total of 790 (2% of the cohort) deaths were documented over 12 months of follow-up, a mortality rate of 2.31 per 100 person-years.

There were 19 deaths in the immediate ART group, a mortality rate of 1.04 per 100 person-years. A total of 58 deaths occurred in the deferred ART group, a mortality rate of 2.25 per 100 person-years. The remaining 713 deaths were documented in the treatment-naïve group, a mortality rate of 2.39 per 100 person-years.

Three-quarters of the deaths were attributed to non-AIDS-related causes. The most common non-AIDS-related cause of death was cardiovascular disease (37%).

Compared to the ART-naïve group, immediate ART provided strong protection against mortality (aHR = 0.37, p < 0.001). Delayed ART also provided modest protection against mortality (aHR = 0.74, p = 0.04).

“In addition to the direct benefit of ART for survival, it is also likely that regular follow up and comprehensive care services associated with ART use contributed to the decreased mortality observed,” suggest the investigators. “After ART initiation, patients entered into the stable care system and received multidisciplinary services including regular medical visits as well as psychosocial support.”

Other factors associated with death were older age (under 50 years vs over 50 years, aHR = 2.03; p < 0.001), being male (aHR = 1.90; p < 0.001), having only a primary education or less (aHR = 1.85; p < 0.001), infection with HIV via heterosexual contact (aHR = 4.16, p < 0.001) or injecting drug use (aHR = 5.07; p < 0.001).

“Our results highlight the significant negative impact of delays in ART initiation in a real-world setting in China,” conclude the authors. “Our results support the urgent need to increase the number of PLWH identified early, and started on effective, long-term ART immediately, as predicted by the UN 90-90-90 targets.”

By Michael Carter

Reference

Zhao Y et al. Immediate antiretroviral therapy decreases mortality among patients with high CD4 counts in China: a nationwide, retrospective cohort study. Clin Infect Dis, online edition, 2017.

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Swiss study examines which years gay men decided to stop consistent condom use http://www.eatg.org/news/swiss-study-examines-which-years-gay-men-decided-to-stop-consistent-condom-use/ Mon, 06 Nov 2017 21:48:47 +0000 http://www.eatg.org/?post_type=news&p=6690 Did new information guide their decisions?

An innovative study presented at the 16th European AIDS Conference (EACS 2017) in Milan two weeks ago used a machine-learning algorithm (originally developed to help astronomers classify galaxies) to tease out whether there were specific groups of gay men within a large national cohort whose sexual risk behaviours followed similar trajectories over time, and if so, whether they were influenced by external factors such as new scientific data.

The analysis of gay men from the Swiss HIV Cohort Study by Luisa Salazar-Vizcaya from the University of Bonn in Germany found that an apparently steady and homogeneous increase in the proportion of men who reported ever having had condomless anal sex with non-steady partners (nscAI) between 2000 and 2016 was in fact due to quite sudden changes in behaviour in three specific groups of gay men who between them numbered less than half of the men in the study. What distinguished the three groups was that their decision to drop 100% condom use with non-steady partners happened at three different time periods.

The study

The Swiss HIV Cohort Study comprises a large majority of all the people diagnosed with HIV in Switzerland. For the purposes of this study, the researches selected a subgroup of 2614 gay men who were diagnosed with HIV and so joined the study between 2000 and 2016. The average length of time men were followed up in the study was nearly nine years and the number of men increased over time, as more were diagnosed than died or dropped out.

Over the cohort as a whole, the proportion of men who said they had ever had nscAI increased from under 20% in 2000 to approximately 60% in 2016. This appeared to be a fairly steady increase, though there was an acceleration in the rate at which men abandoned 100% condom use with non-steady partners after 2008 – the year of the Swiss Statement, the first statement ever publicly issued by researchers about the association between viral undetectability and non-infectiousness.

However, Salazar-Vizcaya emphasised, “Aggregated trends are often over-simplifications”. They therefore used a technique called Hierarchical Agglomerative Clustering to find out whether men clustered into groups that changed behaviour at specific times. This technique, which uses a computer algorithm to generate groups with similarities that are maximal within that group, and minimal between groups, was originally developed by astronomers to sort galaxies into types. The result was a “phylogenetic tree” of behaviour as regards condom use. Phylogenetic trees are more familiar as graphical way of representing genetic differences, but can be used to analyse the degree to which any attribute of individuals within the group is shared by others.

This found that condom usage among about 50% of the men did not change over time. In these individuals, about 25% in any one year reported ever having had condomless anal sex. Note that this actually represents a decrease over time in the frequency of condomless anal sex per individual, because as time goes by, follow-up time increases.

In a second group, comprising 23% of the men, the proportion reporting ever having had nscAI increased steadily from a very low base of about 10% in 2000 to over 90% in 2016. The rate of increase in reported condomless sex took a noticeable turn upwards around 2010.

The other two, smaller groups exhibited much more sudden and dramatic changes in behaviour. In one group, representing 12% of the men, reported nscAI stayed steady at about 10-15% till 2008, then increased steadily to 25% by 2013. After this it took a sudden upward jump to nearly 100% by 2016 – in other words within the space of three years, the situation changed from only one in four of these men answering “yes” to the question “have you ever had condomless anal sex with a non-steady partner?” to nearly all of them answering “yes”.

In the last and smallest group, comprising 9.4% of the men, the situation was even more polarised. This group, numbering roughly 250 men, were historically the most consistent condom users: in any one year only 10% of them reported ever having had nscAI till 2015. Then suddenly, a year later, 95% of them were reported having had nscAI; it was as if this group had, within the space of a single year, taken an en-masse decision to stop using condoms every time.

Further analysis of these groups showed no demographic differences between them in terms of age, ethnicity or education. Only one cluster, the third one, had any distinctive characteristic: its members tended to be more recently diagnosed, with an average date of diagnosis of November 2012 and a quarter of them diagnosed since the mid-2015 (though another quarter were diagnosed before 2005).

Although this is speculative, Luisa Salazar-Vizcaya hypothesised that the second group were people who from 2001 or so onwards were trying to use ‘serosorting’ as a method of avoiding transmitting HIV. An increase in the rate of their reporting nscAI occurred around 2008, the year of the Swiss Statement, as did the first increase in condomless sex reported by group 3. The sudden jump in condomless sex in group 3 happened at around the same time as the first results of the PARTNER study – findings that were widely reported in the gay media. Finally, the sudden increase in condomless sex in group 4 coincides with the publication of the results of the PROUD and IPERGAY pre-exposure prophylaxis (PrEP) studies. Were these men – who had previously been the most consistent condom users – ones who had negative partners who started taking PrEP?

These remain speculations at present, and Salazar-Vizcaya said that qualitative research was needed to discover whether changes in condom use in different men were associated with different findings being publicised.

As a general point, she added, the study showed that it was a mistake to assume homogeneity of behavioural change and therefore of motivations for change in cohorts under study: similar analyses could help to identify how different pieces of knowledge and thought processes influenced different groups, which could lead to more precision and effectiveness when it came to spreading positive health messages.

By Gus Cairns

Reference

Salazar-Vizcaya L et al. Highly Dissimilar Patterns of Sexual Risk Behaviour among HIV-positive Men who Have Sex with Men: Clustering Individual Trajectories in the Swiss HIV Cohort Study from 2000 to 2017. 16th European AIDS Conference, October 25-27, Milan, abstract PS12/1, 2017.

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HIV Outcomes Conference in Brussels – Register Now http://www.eatg.org/news/hiv-outcomes-conference-in-brussels-register-now/ Fri, 03 Nov 2017 17:10:05 +0000 http://www.eatg.org/?post_type=news&p=6649 On behalf of the multi-stakeholder initiative “HIV Outcomes: Beyond viral suppression”, you are warmly invited to attend the launch of the initiative’s recommendations on “Long-term health, well-being, and chronic care for people living with HIV (PLHIV)”, which will take place at the European Parliament in Brussels on 29 November (13:00-15:00).

The HIV Outcomes initiative reflects a widespread conviction among HIV experts and those living with HIV that important issues relating to the long-term health and quality of life of PLHIV currently receive insufficient attention at the policy level. Launched ahead of World AIDS Day on 1 December, the HIV Outcomes recommendations will focus on improving health system responsiveness to these challenges, and the need to strengthen monitoring of health system performance in that context.

The opening part of the meeting will feature patient, clinician and policy perspectives on the above challenges. WHO Europe will discuss how the work of the initiative corresponds to wider health system responses to the increasing burden of chronic disease and comorbidities in Europe. This will be followed by the presentation of the HIV Outcomes initiative recommendations on long-term health, well-being and chronic care for PLHIV, which are intended to inform thinking at the national level.

The second half of the meeting will focus on the need for continued political action on HIV/AIDS.European Commissioner for Health, Vytenis Andriukaitis, will give the keynote address focusing on EU action in relation to HIV/AIDS. He will be followed by Ricardo Baptista Leite, Founding President of UNITE – the Parliamentarians Network to End HIV/AIDS, Viral Hepatitis and Tuberculosis – who will update us on the work and progress of UNITE.

The agenda for the meeting is available here. The event is supported by MEPs Christofer Fjellner from the European People’s Party (Sweden), Eva Kaili from the Socialists and Democrats (Greece) and Gesine Meissner from the Alliance of Liberals and Democrats for Europe (Germany).

This initiative comprises stakeholders from across the HIV community – patients, healthcare professionals, academics and industry (a full list of Steering Group members is provided below). As it is enabled by sponsorship from Gilead Sciences and ViiV Healthcare, the attached principles of engagement contain terms and conditions relating to your participation in this meeting and compliance with relevant industry codes. Please read them carefully.

If you have any questions, please contact us at HIVoutcomes.secretariat@gmail.com. You can also contact Hannah Garrett (secretariat) on +32 2 613 28 28. ]]> The Lancet on U=U http://www.eatg.org/news/the-lancet-on-uu/ Fri, 03 Nov 2017 14:24:08 +0000 http://www.eatg.org/?post_type=news&p=6646 This editorial was published in The Lancet on 4 November 2017. Following previous communications from the CDC of the USA and other scientific sources, The Lancet now also confirms that the evidence is conclusive: People living with HIV who have an undetectable viral load do not transmit the virus through sexual contact. 

The fact that people infected with HIV who are virally suppressed cannot sexually transmit the virus to others is now accepted in the HIV/AIDS community as a result of accumulating evidence since the early 2000s. In early 2016, the Undetectable=Untransmissable (U=U) slogan was launched by the Prevention Access Campaign to promote the finding. The campaign has been rapidly gathering momentum, having been endorsed by more than 400 organisations from 60 different countries since its launch. Last month, the US Centers for Disease Control and Prevention (CDC) joined the movement by endorsing the science in a letter released on National Gay Men’s HIV/AIDS Awareness Day.

The evidence to support the effectiveness of viral suppression in blocking transmission is clear. In addition to some smaller studies done since 2000, three larger studies of sexual HIV transmission in thousands of serodiscordant couples including thousands of acts of sex were done between 2007 and 2016, with, strikingly, not a single case of sexual transmission of HIV from a virally suppressed HIV-positive person to their HIVnegative partner reported. The HPTN 052 trial, the largest study to date, studied 1763 serodiscordant couples (both homosexual and heterosexual) from nine different countries and randomly assigned HIV-positive participants to either early or delayed antiretroviral treatment (ART). Interim results published in 2011 showed that 39 HIV-negative partners had become HIV positive so far, of which 28 were phylogenetically linked (ie, 28 people acquired their infection from their partner). Of these 28, only one occurred in the early ART group. After this analysis, ART was then offered to all patients with HIV and all patients continued to be followed up to 2015, with the final results published in September last year. Over the entire course of the study, 78 infections were observed, of which phylogenetic linkage was established in 72. Of these infections, 46 were linked to the HIV-positive partner, eight of which occurred after the partner commenced antiretroviral therapy. Of these final eight, four occurred before viral suppression and the other four occurred when ART failed to achieve viral suppression. In other words, not one virally suppressed HIV-positive patient transmitted their infection to their partner during the entire study. The PARTNER study, published in July last year, was an observational study of 1166 HIV-serodiscordant couples (also both homosexual and heterosexual) from 14 countries across Europe with more than 58000 instances of unprotected sex reported. Although 11 HIV-negative partners became HIV positive, none of these transmissions were linked. Finally, results of the most recent study, the Opposites Attract study, were presented this July at the 9th International AIDS Society Conference on HIV Science in Paris. This cohort study followed up 358 homosexual men with HIV from three different countries with about 17000 acts of sex taking place. Three new cases of HIV infection were observed but, as expected, none of these infections were linked either. The fact that HIV treatment has advanced to the point that people infected with HIV can live full-length, healthy lives with zero chance of sexually transmitting the virus to others as long as they are on effective ART is a huge success.

Although evidence for this fact has been growing since 2000, it has been slow to influence public perception. However, the U=U campaign, launched just under 2 years ago now, has been directly tasked with tackling this unfortunate public ignorance, and to flying success in its fairly short lifespan to date. The slogan embodies the idea of treatment as prevention. This idea has been around since at least 2010, but since the easy to-grasp U=U slogan has been established, the concept has been firmly pushed into the public sphere and has been a major talking point in the HIV/AIDS community this year. The CDC officially backing the science behind the campaign is another key step towards U=U being the most important message of 2017 in the fight against HIV.

U=U is a simple but hugely important campaign based on a solid foundation of scientific evidence. It has already been successful in influencing public opinion, causing more people with HIV (and their friends and families) to comprehend that they can live long, healthy lives, have children, and never have to worry about passing on their infection to others. The clarity of the message will make it easier to promote the undeniable benefits of treatment, which will encourage more and more people with HIV to seek treatment, bringing the HIV community one step closer to achievement of the UNAIDS’ 90-90-90 target by 2020 and to complete elimination of the entirely unfair and outdated stigma still faced by many people living with HIV today. ■ The Lancet HIV

Download The Lancet editorial here: LANCET U=U 11 2017

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CoPE Call for Applications http://www.eatg.org/news/cope-call-for-applications/ Fri, 03 Nov 2017 09:25:11 +0000 http://www.eatg.org/?post_type=news&p=6645 We are pleased to announce a special CoPE call for hepatitis, addressing the need for access to hepatitis prevention, testing, treatment and care services by co-infected key populations. Please find below detailed information on how to apply for this grant. The submission deadline is Monday 30 November 2017 (23:59 CET).

What is CoPE?
The CoPE project is a funding mechanism that enables the production and translation of patient education materials, brochures and other resources related to HIV/AIDS & co-infections in multiple languages. More information about CoPE can be accessed here: www.eatgtrainingacademy.com/cope.

Who can apply and receive a grant?

Any community-based organisation in the European and Central Asian region dealing with prevention and treatment of HIV/AIDS and co-infections can submit an application to CoPE. The selection is based on the soundness of the proposed project and available funding.

What type of publications are supported?
CoPE supports publications which:

  • Promote necessary, objective, reliable and up-to-date knowledge and skills about HIV/AIDS and co-infections among patients, patient groups, groups at-risk, and healthcare providers;

  • Raise awareness and appreciation of facts and issues related to HIV/AIDS treatment among PLWH (such as women, men who have sex with men, injecting drug users, sex workers, migrant communities and other groups at-risk);

  • Offer objective, scientifically-accurate, high-quality, patient-focused and user-friendly overview and summary of relevant health and treatment information on specific and generic HIV-related topics and issues;

  • Engage, support and empower local HIV-positive community for the preparation and development of necessary and relevant treatment materials.

  • The final format of the resource may be a printed brochure, booklet, handout etc. or an online document/website.

Specific focus for this call
This call is specifically focused on the topic below. Applications dealing with other topics will not be considered during the selection process.

  • Applications addressing the need for access to hepatitis prevention, testing, treatment and care services by co-infected key populations. This includes publications that support the local community in better understanding HCV and HBV as co-infections.  

Application procedure
Please fill in and submit an application form online via this link:
www.eatgtrainingacademy.com/application-form.
Please fill in all the sections of the application form in English. Incomplete applications will not be considered.

Submission Deadline
The deadline for submission is Monday 30 November 2017 (23:59 CET).

Notification of selection outcome
The outcome of your application will be announced five weeks after the submission deadline.

Before applying

  • Map the existing resources in the local language and in English/other languages. An archive of the materials previously funded by CoPE is available here.

  • Define if you would like to translate an existing publication or develop something entirely new.

    • For a translation, ask for authorization from the original author for the use of the material. Specify the eventual changes you would like to make to the original (adapting it to the local context).

    • For a new publication, develop a summary of the main topics and themes covered. Make sure you have access to leading expert(s) in the field who can guarantee the accuracy of the information.

  • Make a detailed cost estimate of the cost of production of the publication, including writing/translating, proofreading, design & layout, printing and dissemination. The estimate should be based on actual quotes from different service providers. Please note that, if accepted, the CoPE grant is paid in two instalments: first 50% when a print-ready document is submitted and the remaining amount upon receipt of financial and narrative reports (incl. copies of all invoices and receipts).

  • Please note that the maximum amount that is available for this call is 1,100 EUR. Applications requesting lower amounts will be considered favourably in the selection process.

  • Make a realistic timeline for the production process. Please note that, if accepted, the project should be finalized within 3 months (for translations) or 6 months (for new publications) from the signing of the grant agreement. The final grant amount may be decreased in case of delay caused by the grantee. Therefore, make sure you and your collaborators are ready to start working instantaneously if your application is approved.

  • Draft a dissemination plan. The publication should be widely promoted (locally, regionally and nationally) via different channels.

Questions:
If you have any questions regarding the CoPE project or the application form please contact Maria Dutarte (EATG Project Manager) at projects@eatg.org.

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World Hepatitis Summit – Declaration of the Hepatitis Community http://www.eatg.org/news/world-hepatitis-summit-declaration-of-the-hepatitis-community/ Thu, 02 Nov 2017 22:52:18 +0000 http://www.eatg.org/?post_type=news&p=6638 The World Hepatitis Summit passed and published the Declaration of the Hepatitis Community “NO ELIMINATION WITHOUT DECRIMINALIZATION!” today. The Declaration calls for the decriminalization of people who use drugs, and the global upscale and support of prevention, harm reduction and treatment services available to them.

It urges states “to remove all barriers to the uptake of the full range of prevention services by people who use drugs by reforming laws, law enforcement procedures and discrimination that hinder access, including the criminalization of minor, non-violent drug offences and to adopt an approach based overwhelmingly on public health promotion, respect for human rights and evidence”.

The consortium of signatories was led by Medecins du Monde, and EATG has also been a member.

Declaration website: http://www.medecinsdumonde.org/en/actualites/hepatite-c/2017/10/31/hepatitis-no-elimination-without-decriminalization

Declaration in French: Hepatitis-declaration-FR

Declaration in English: Hepatitis-declaration-EN

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Report: TB medicine crisis in Romania http://www.eatg.org/news/report-tb-medicine-crisis-in-romania/ Thu, 02 Nov 2017 22:24:16 +0000 http://www.eatg.org/?post_type=news&p=6642

Authorities in Romania are unable to provide the full range of essential medicines needed for the treatment of TB, the Romanian Health Observatory said in its latest report, TB medicine crisis in Romania. While the contagious disease is designated a public health priority in the country, the root cause is “the existence of absurd and self-contradictory legislation and widespread government red tape” that blocks Romanian tuberculosis patients’ access to treatment, it said.

Missing meds: From 28 drugs considered necessary for treatment by the World Health Organization or Romania’s national prevention program, 15 are unavailable or have supply disruptions. One medicine not reimbursed for tuberculosis is reimbursed for HIV. “Practically, patients diagnosed with HIV and TB are more fortunate than patients who have only a diagnosis of tuberculosis,” the report observed. Meanwhile, the fact that only some drugs are available could increase prevalence of multidrug-resistant tuberculosis if patients end up taking an incomplete treatment. With more than 500 new cases of drug-resistant tuberculosis detected annually, Romania has the highest number of cases in the EU but one of the lowest rates of successful management.

At this point, international organizations are providing and co-financing the procurement of essential medicines needed for Romanian TB patients. The international funding will end in the first quarter of 2018. The patients will be left without access to the full course of treatment if the Romanian authorities will not be able to take over the procurement. Currently, the Government of Romania – an European Union member state – is not fulfilling its legal obligations towards TB patients.

A summary of the report in English can be downloaded here.

The full version of the report can be accessed here (in English) and here (in Romanian).

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November 2017 issue of The Lancet HIV now online http://www.eatg.org/news/november-2017-issue-of-the-lancet-hiv-now-online/ Thu, 02 Nov 2017 21:11:45 +0000 http://www.eatg.org/?post_type=news&p=6644 The Lancet HIV is an exclusively online journal dedicated to publishing original research that advocates change in, or illuminates, HIV clinical practice. It publishes translational, epidemiological, clinical, operational, and implementation studies.

The November 2017 issue is available here.

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