News | EATG http://www.eatg.org European AIDS Treatment Group Mon, 22 Jan 2018 21:28:51 +0000 en-US hourly 1 https://wordpress.org/?v=4.8 Shining a light on trans women’s needs in sub-Sarahan Africa http://www.eatg.org/news/shining-a-light-on-trans-womens-needs-in-sub-sarahan-africa/ Mon, 22 Jan 2018 21:27:52 +0000 http://www.eatg.org/?post_type=news&p=7240 New research marks welcome step to make trans women in sub-Saharan Africa visible in HIV data.

Across Sub-Saharan Africa, where HIV epidemics are generalised across the population, transgender women have long been overlooked as a community with particular sexual health needs.

Instead of investigating their particular needs, transgender women are often analysed within the same category as cis-gender men who have sex with men (sometimes known as MSM).

A new study published in PLOS Medicine reveals how this is hiding specific drivers of HIV within this community, and ignoring important differences in experiences between these two groups.

The researchers analysed previously published data from 14 sites across eight countries in Africa, including Côte d’Ivoire, Senegal, Swaziland, Burkina Faso, Malawi, Lesotho, Togo, and The Gambia. The included studies all compared HIV prevalence as well as social and behavioural drivers of infection in transgender women and cis-gender MSM.

Although HIV prevalence varied significantly across the countries, the study found that on average transgender women were 2.2 times more likely to be living with HIV than cis-MSM. In some countries, this difference was even more pronounced, for example in Lesotho transgender women were 3.6 times more likely to have HIV, with a prevalence rate of 59%.

Although there were some bio-behavioural differences between the two groups, with transgender women reporting more condomless receptive anal sex, this was not able to fully explain the differences in HIV prevalence between the two genders, especially since transgender women reported greater access to condoms when they needed them and were more likely to have tested for HIV in the last 12 months.

Instead, the researchers point to social factors as being the main cause of these differences in HIV prevalence between the two groups. Although they found that both groups had experienced high levels of stigma – with many respondents of both genders reporting fear of seeking health services and loss of employment or educational opportunity due to their sexual orientation or gender identity, transgender women were more likely to have experienced family exclusion, rape and symptoms of depression than cis-gender MSM (despite depressive symptoms and suicidal ideation being common in both groups).

This is the first study to shine a light on the role that gender identity plays in the HIV epidemics of Sub-Saharan Africa. It shows that, like elsewhere in the world, there is an unmet need for HIV prevention and care for transgender people. Despite the World Health Organization (WHO) having stated that the ‘specific health needs of transgender people necessitates a distinct and independent status in the global HIV response’, only 39% of countries specifically address transgender people in their HIV strategies.

The authors comment that research like this is crucial for making ‘transgender participants visible within the data’ and that this is a crucial first step in providing services that are gender affirming and speak to the needs of trans people.

In a previous interview with Avert, trans activist Marcela Romero commented that across the world, ‘trans women are being lost in a system that still believes that they are men’. She stated along with Mitch Yusof, a trans activist from Malaysia that: ‘With data, we will be able to argue our position in society, to provide the evidence that we are part of the wider community’.

By Francesca Harrington-Edmans

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Managing the fruits of HCV cure: how much care do the cured need? http://www.eatg.org/news/managing-the-fruits-of-hcv-cure-how-much-care-do-the-cured-need/ Mon, 22 Jan 2018 21:18:32 +0000 http://www.eatg.org/?post_type=news&p=7239 The feature by Eric Lawitz, MD, very nicely encapsulates the revolutionary changes occurring within hepatitis C therapy over the past few years. As he explains, this extraordinary newfound ability to cure almost all patients with chronic HCV raises many questions about clinical outcomes.

We’ve felt strongly for years that it was unjust to deny therapy to patients who didn’t have “sufficiently advanced scarring of the liver to warrant treatment” — a cost-based position that was anathema to most clinicians and patients. Today, there’s a wealth of literature showing fibrosis progression stabilizes or reverses after achieving SVR. Even patients with cirrhosis may have regression of cirrhosis after SVR. But an additional dimension of HCV infection about which our knowledge has dramatically expanded is the potential for extrahepatic morbidity and mortality associated with HCV infection, and the opportunity to ameliorate or prevent such outcomes by effecting virologic cure — problems such as diabetes, atherosclerosis, renal disease, cryoglobulinemia, lymphoma and others.

All of this raises the question of how to manage cured patients.

Though treatment choice is still an important decision, practitioner focus now shifts from which regimen to use (as there are several of extraordinary efficacy that are all well tolerated, albeit with some nuances that differentiate them, such as duration of therapy, potential drug-drug interactions and regimen-dependent need for ribavirin in some subpopulations), to wondering with increasing frequency what to do with the patients once we cure them.

We became familiar with this topic in the interferon era but now that this occurs so much more frequently, it becomes a question that can arise multiple times daily in a busy HCV-oriented practice. It’s important for us to link data regarding clinical outcomes after cure with management decisions about patients who may still be at risk for complications.

HCC Risk Management

Of all the complications of liver disease, one of the most dreaded is hepatocellular carcinoma. Just as we’ve been gratified to learn that SVR brings a marked reduction in the risk for HCC, so we have also come to recognize the risk is far from negligible in patients with cirrhosis who have been cured and, to a lesser extent, in patients with advanced fibrosis short of cirrhosis.

Because of the lingering risk for HCC in cirrhotic patients after cure of HCV infection, the general rule that has arisen is that you must screen such patients every 6 months with imaging and optional alpha-fetoprotein determinations indefinitely. Some clinicians have voiced uncertainty about whether indefinite surveillance is too much of a burden to impose on patients when their risk may become progressively smaller to the point where it might not be ‘cost effective’ to continue to screen. I have heard a few colleagues suggest that if cirrhosis is no longer present based on parameters such as tissue elastography (eg, Fibroscan [Echosens] or other modalities), then perhaps we can stop screening. I regard this at present as a potentially risky proposition. We don’t yet have sufficiently robust data to suggest we have an identifiable parameter that says that the patient who was cirrhotic before treatment is no longer at material risk for liver cancer.

Speaking for myself and many other colleagues, who as I perceive it comprise the great majority of the field, we still should be screening these patients indefinitely.

I’m hopeful the day will come when we can point to multi-thousand patient databases that pinpoint a certain degree of improvement in fibrosis or cirrhosis in an identifiable parameter like elastography or perhaps a serum marker as a benchmark for cancer risk. We would then need large numbers of patient-years of follow up to say that the risk for cancer regresses to a level comparable to that of the background population.

The question arises as to what degree of fibrosis prior to treatment obviates the need for further follow up. Most society guidelines state that if you have F0 to F2 fibrosis, you don’t have to be screened. By and large, I am comfortable with that, but there are sporadic case reports and large series from Japan suggesting that there is a small, but not negligible, risk for liver cancer, particularly in patients with F2 fibrosis. These series don’t always make it clear whether patients may have had concomitant causes of progressive liver disease, but they do occasionally report cases of patients who did not have cirrhosis at the time their HCC was discovered.

My own practice is to get an ultrasound within a year of finishing therapy for patients and, if there’s no pre-treatment evidence that patients had Metavir F3 or F4 fibrosis, to stop subsequent screening, hoping the day never comes when I must face a patient who had mild fibrosis who in fact develops HCC.

My opinion is to keep screening your patients who had advanced fibrosis prior to their course of curative therapy. We are not there yet in determining a stopping point.

Stability vs. Regression

Patients familiar with Fibroscan frequently request the procedure after they’re cured before I even bring it up. I’m struck by how important it is for virologically cured patients to not only feel that their fibrosis has stabilized, which is a concept that I emphasize, but are understandably very attuned to getting the “fringe benefit” of fibrosis reversal.

I do tell patients that if their Fibroscan proves to be unchanged, not to stop exulting over the fact that they have eliminated their HCV infection. It does virtually ensure, in the absence of another liver disease, that they won’t progress to decompensation, and their risks for coming to harm are still greatly diminished even as they continue to need HCC screening.

Esophageal Varices

The other issue that arises is whether to continue screening patients for esophageal varices if they presented with cirrhosis. We have been gratified to find over the years that it’s quite unusual to have patients have a variceal bleed after they’ve had an SVR, but it can occur.

We continue to need to be on guard against the dreaded complication of variceal bleeding. In my practice, if patients have had no varices previously, I usually do another endoscopy within 1 to 2 years following SVR. If they still have no varices, which is generally the case, we can cease and desist from further endoscopic evaluation unless they have a concomitant liver disease manifested by an elevated alanine aminotransferase or other evidence of ongoing liver injury. In my experience, the most common cause for ongoing liver disease in patients cured of HCV infection is fatty liver disease. For varices too small to consider primary prophylaxis previously, endoscopic surveillance should continue.

If patients have varices that needed to be medically managed previously with beta blockers and/or variceal band ligation, that management must continue until and unless the varices have been shown to regress over repeated examinations. Recent evidence points to potential for portal hypertension to regress, but there is no assurance in any individual case that it will occur. Certainly, for patients who have had a variceal bleed, they continue to need the combination of periodic endoscopy with band ligation and beta blockade if they can tolerate beta blocker therapy.

We need more data on the long-term outcome of varices and portal hypertension in general. Quantitative data on the rate of variceal regression can better inform our decision about when we can stop performing endoscopic surveillance or in these patients.

Alcohol Consumption

Many patients ask about alcohol consumption after being cured. For most hepatologists, any alcohol consumption with preexisting cirrhosis is forbidden, but I think we can relax our previous restrictions if patients had demonstrable mild or even moderate liver disease. This is predicated on the assumption we’ve gotten to know the patient sufficiently well to be confident they are representing to us accurately their degree of alcohol intake.

For patients who have had problems with excessive drinking in the past, you can strongly recommend that complete abstention remains the rule.

These comments are a combination of subjective opinion based on practice and experience along with literature as we are just starting to see robust data sets emerging from large multisystem studies quantifying the degree of decreased hepatic and extrahepatic morbidity and mortality achieved due to SVR. These types of studies have been illustrated at the AASLD meeting where we’re beginning to see large data sets of clinical outcomes patients after DAA therapy that amplify greatly upon the data that we developed in the age of interferon.

We look forward to further studies as clinical researchers shift gears from the development of new drugs to important global issues like access and cost, but also to clinical outcomes studies. With the emerging information about these critical issues that will likely predominate at academic meetings and in the literature in the near future, we can optimally inform our decision-making about how to manage cured patients.

By Ira M. Jacobson, MD

References:

Jacobson IM, et al. Gastroenterology.2017;doi:10.1053/j.gastro.2017.03.018.

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Smoking causes one in five cancers in people with HIV in North America http://www.eatg.org/news/smoking-causes-one-in-five-cancers-in-people-with-hiv-in-north-america/ Mon, 22 Jan 2018 21:05:00 +0000 http://www.eatg.org/?post_type=news&p=7238

A fifth of all cancers in people receiving HIV care in North America between 2000 and 2015 was due to smoking, according to US research published this month in advance online by the journal AIDS.

“In the United States, the prevalence of smoking among HIV-infected people is substantially higher than in the general population, and most HIV-infected individuals either currently smoke or have previously smoked,” comment the authors. “Our findings indicated that a substantial fraction of cancer diagnoses among HIV-infected individuals potentially would not have occurred if they had never smoked.”

Thanks to improvements in HIV treatment and care, most people with HIV now have a normal or near-normal life expectancy. As these people age, non-AIDS-related cancers are an important cause of death.

Smoking tobacco can cause a range of cancers including lung cancer and its role in the development of cancers of the oral cavity, larynx, liver, colon, rectum and kidney is well established. Smoking may also contribute to the development of other cancers but more research is needed to understand how it might contribute to the development of these cancers. Smoking was estimated to cause 29% of all cancer deaths in 2010 in the United States.

Research conducted in 2009 suggested that 42% of people with HIV in the United States were current smokers and a further 20% were former smokers, twice the rate seen in the general population. Given this high prevalence of smoking, a team of investigators designed a study to estimate the cancer risk associated with smoking and the proportion of cancers due to smoking.

The study sample included 52,441 people who received HIV care in North America between 2000 and 2015 and for whom records of smoking habits were available. Most were taking antiretrovirals.

The investigators first calculated the relationship between smoking and cancer risk and then examined the proportion of cancers attributable to smoking.

The patients contributed a total of 270,000 person-years of follow-up, a median of 3.8 years per person. A new cancer was diagnosed in 2306 people (4%), an incidence of 8.53 per 1000 person-years.

People with cancer were significantly more likely to have smoked (79% of people who developed cancer vs 73% of people who did not develop cancer had smoked at some time, p < 0.001).

After controlling for other risk factors, ever smoking was associated with a significant increase in the risk of any cancer (aHR = 1.33; 95% CI: 1.18-1.49) and a doubling (aHR = 2.31; 95% CI, 1.80-2.98) in the risk of a smoking-related cancer (such as cancer of the lung, larynx, liver, colon, rectum, oral cavity, kidney, cervix and leukemia). Smoking did not, however, significantly increase the risk of non-smoking-related cancers.

Of the smoking-related cancers, the association was strongest for lung cancer (aHR = 17.80; 95% CI, 5.60-56.63) and was also significant for other smoking-related cancers (aHR = 1.59; 95% CI, 1.22-2.06). Smoking also significantly increased the risk of anal cancer (aHR = 1.57; 95% 1.08-2.28).

The investigators estimated that 19% of all cancers were due to smoking, including 50% of smoking-related cancers and 9% of non-smoking-related cancers. Almost all cases of lung cancer (94%) were attributed to smoking, as were 32% of all cases of anal cancer. (In this study population anal cancer was diagnosed almost as frequently as lung cancer.)

“Compared to never smokers, the risk of a smoking-related cancer diagnosis was more than twice as high among those who ever smoked, and the risk of a lung cancer was nearly 18 times as high,” write the investigators. “Approximately one-fifth of cancer diagnoses in this population were potentially attributed to smoking, including 50% of smoking-related cancers and 94% of lung cancer diagnoses.”

Although the proportion of cancers caused by smoking is lower in people with HIV than in the general population, the authors say that this is explained by the fact that 12% of all cancers diagnosed in people with HIV were Kaposi’s sarcoma, which is very rare in people without HIV and not related to smoking.

The authors call for the prioritisation of smoking prevention and cessation services. They point out that quitting smoking is associated with a reduction in the risk of developing smoking-related cancers.

“Since many HIV-infected smokers are motived to quit, health care providers can assist HIV-infected people with smoking cessation at repeated clinical encounters by offering behavioral and pharmacologic interventions,” suggest the investigators. “High quality resources exist specifically to assist HIV care providers in helping their patients to quit smoking.”

By Michael Carter

References

Altekruse SF et al. Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS, online edition. DOI: 10.1097/QAD.0000000000001721 (2018).

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HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection http://www.eatg.org/news/hiv-1-genetic-diversity-is-higher-in-vaginal-tract-than-in-blood-during-early-infection/ Thu, 18 Jan 2018 22:59:49 +0000 http://www.eatg.org/?post_type=news&p=7229 A first-of-its-kind study has found that the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is higher in the vaginal tract than in the blood stream during early infection. This finding, published in PLOS Pathogens, supports the existence of a genetic bottleneck between the vaginal tract and the bloodstream.

When HIV-1 is transmitted from a man to a woman via intercourse, it must penetrate and infect various vaginal layers before reaching the blood. Previous research has shown that, within a patient, systemic infection is usually established by a single genetic variant of HIV-1 in the blood. However, scientists hypothesize, the vaginal tract may initially harbor a genetically diverse HIV-1 population that is then filtered down to a single variant along the path to the blood stream.

To better understand this potential genetic bottleneck, Katja Klein of the University of Western Ontario, Canada, and colleagues conducted the first study to compare HIV-1 genetic diversity between the vaginal tract and the blood in newly infected people. They collected and applied next-generation deep sequencing to HIV-1 viruses isolated from the vaginal tract and blood plasma of 75 Ugandan and Zimbabwean women within seven months of infection.

This analysis revealed that each patient’s vaginal tract generally harbored a diverse range of HIV-1 genetic variants (a mean of 5.7), while the blood had much lower genetic diversity (a mean of 1.7 variants). These results held true regardless of a patient’s HIV-1 subtype, use of hormonal contraceptives, or number of sex acts or partners.

All samples in the study were collected at least one month after initial infection, and the authors acknowledge the possibility that genetic diversity in the vaginal tract may have arisen post-infection. However, they point out that this is unlikely, given that similar diversification was not seen in the blood stream.

These findings present new evidence in support of the idea that a genetic bottleneck winnows out many genetic variants of HIV-1 between the vaginal tract and the blood during early infection. This could improve understanding of the transmission process, thereby informing efforts to develop vaccines and other therapies to prevent against HIV-1 infection.

“As observed with many infectious pathogens and diseases, our mucosal layers have evolved to produce protective molecules, accommodate good microbes and keep the bad ones out of our blood stream,” the authors explain. “Obtaining samples from the female genital tract in cases of new HIV infection will always be difficult but these studies could be crucial in understanding the design and efficacy of HIV vaccines and other prevention strategies.”

Klein K, Nickel G, Nankya I, Kyeyune F, Demers K, Ndashimye E, et al. (2018) Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection. PLoS Pathog 14(1): e1006754. doi.org/10.1371/journal.ppat.1006754

 

Read also:

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Antibodies show effectiveness for HIV prevention and promise for treatment and cure http://www.eatg.org/news/antibodies-show-effectiveness-for-hiv-prevention-and-promise-for-treatment-and-cure/ Thu, 18 Jan 2018 22:55:57 +0000 http://www.eatg.org/?post_type=news&p=7231 The ability of HIV to mutate has been a major challenge to vaccine development. As the body produces antibodies to target the outer HIV envelope protein, this protein changes, thwarting the circulating antibodies’ ability to neutralize it. Yet recent studies testing multivalent combinations of three broadly neutralizing antibodies, or bnAbs, have yielded promising results in animal models of HIV prevention. Two investigators at the University of North Carolina at Chapel Hill describe the potential of bnAbs to inform HIV prevention, treatment and cure strategies in a recent article in the New England Journal of Medicine.

“BnAbs are thought to be akin to signposts – that they point to a path that might be followed by a future HIV vaccine strategy through induction of bnAbs capable of preventing HIV infection,” said David Margolis, M.D., article co-author and director of the UNC HIV Cure Center.

No single bnAb can protect against all the variants of HIV present in infected individuals. However, combinations of multiple bnAbs provide increased efficacy. The development of trispecific multivalent antibodies combine the best attributes of each into a single molecule capable of recognizing and neutralizing multiple viruses not recognized by the individual bnAbs.

“Trispecific antibodies engage a broader range of viral particles than do monospecific and bispecific antibodies,” said J. Victor Garcia, Ph.D., article co-author and a professor of medicine at UNC. “Trispecific antibodies may also block infection more efficiently at mucosal surfaces and within deeper tissue as well as neutralize a wider range of viral particles.”

The authors also detail how bnAbs could change HIV treatment and cure research. Broadly neutralizing antibodies may contribute to the deployment of long-acting antiretroviral therapy, which would be an attractive alternative for people who currently take daily medication to control their HIV. In the cure arena, bnAbs could be paired with latency reversing agents to target and clear the virus.

“Broadly neutralizing antibodies capable of recognizing HIV-infected cells could direct effector cells to clear the latent reservoir,” Margolis said. “In the case of the evasive HIV envelope, three may be the charm.”

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Cancer gene therapy strategy suppresses HIV in lab study http://www.eatg.org/news/cancer-gene-therapy-strategy-suppresses-hiv-in-lab-study/ Thu, 18 Jan 2018 22:41:06 +0000 http://www.eatg.org/?post_type=news&p=7232 The first FDA-approved gene therapy treatment for cancer patients has shown promise in suppressing HIV infection long term in lab monkeys, according to a study partially funded by amfAR.

Researchers genetically engineered stem cells to express chimeric antigen receptors (CAR) that can detect and destroy SHIV (a combination of HIV and SIV—the monkey form of the virus). The cells were then tested in four male juvenile SHIV-infected macaques.

Not only did the engineered cells decrease the viral load, they persisted for more than two years in the monkeys without any adverse effects. Furthermore, the cells were widely distributed throughout the lymph nodes and gastrointestinal tract, where viral replication and persistence are concentrated.

“The advantage of the stem cell-based approach is that once these cells are grafted into the body, they continuously produce new T cells that have this gene in them that can target HIV cells,” said amfAR grantee Dr. Scott Kitchen of the University of California, Los Angeles.

The FDA approved the gene therapy treatment Kymriah in August 2017 for young people up to age 25 with a form of acute lymphoblastic leukemia, a blood cancer. The therapy involves modifying a patient’s own T cells and genetically engineering them with CAR cells that can recognize and kill tumors.

Its approval coincided with the announcement of two amfAR grants exploring a similar strategy to curing HIV.

Commenting on the study for HealthDay, Dr. Marcella Flores, amfAR’s associate director of research, said she was cautiously optimistic about the potential of gene therapy to eradicate the virus. “CAR therapy is already leading to impressive results in cancer,” she said.

However, she noted that the study was performed in monkeys. Results in humans may be quite different.

Kitchen said human trials could begin within two to three years. While it is unlikely that the CAR strategy will work completely on its own, he said it could be used with antiretroviral therapy to engineer an immune response to target and kill HIV.

“Theoretically the goal is to provide lifelong immunity to HIV,” he said. “We’re aiming for a cure, and we know that to cure HIV you need an effective immune response.”

The study was published in the December 28 issue of PLOS Pathogens.

See also: Using Groundbreaking CAR-T Cancer Therapy to Eliminate HIV

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PrEP’s social impact on the lives of some gay men in Toronto http://www.eatg.org/news/preps-social-impact-on-the-lives-of-some-gay-men-in-toronto/ Thu, 18 Jan 2018 22:30:17 +0000 http://www.eatg.org/?post_type=news&p=7233

— Researchers interviewed early adopters of PrEP in Toronto about their experience.
— Participants reported that their use of PrEP left them feeling “proud” and “liberated.”
— Stigma and judgment related to PrEP also led some participants to conceal their use of it.

PrEP (pre-exposure prophylaxis) involves taking two anti-HIV medicines in one pill, usually daily, to reduce the chance of getting HIV. PrEP is meant to be used in combination with other HIV prevention approaches, such as the following:

  • risk reduction counselling
  • use of condoms
  • regular testing for HIV
  • screening for sexually transmitted infections and, if necessary, treatment

Detailed information about the use of PrEP can be found here.

Researchers in Toronto conducted a PrEP demonstration project to assess its acceptability, use and effectiveness among 52 gay, bisexual and other men who have sex with men (MSM). Part of this project involved interviewing a subset of participants about the impact of PrEP on their social and sexual lives. From these interviews, researchers found that a large proportion of men felt the need to conceal their use of PrEP from friends, family and sexual partners because of attitudes toward PrEP use. When the men disclosed their use of PrEP, it usually resulted in some degree of negative and complex reactions in their social networks. However, PrEP also allowed the men to experience a sense of normalcy during sex; they found sex free of fear, and, as a result, sex became “exciting and pleasurable.”

Study details

Participants were recruited from a study called Preparatory-5. Prior to being interviewed, participants had been taking PrEP for at least one year between November 2014 and June 2016. Sixteen of the participants agreed to be interviewed. The men were white and gay-identified and their average age was 33 years.

Results—A feeling of liberation

Many participants said that their use of PrEP left them feeling “proud” and “liberated.” According to the researchers, “This idea of pride in being a responsible sexually active gay man and helping to prevent the spread of HIV was a recurrent theme in the men’s accounts.”

One participant stated the following about his PrEP experience:

“It has been one of the greatest things in my life. I have absolutely loved it. I have a lot of sex, and I go to the bathhouses a lot, despite my advanced age…. For the first time in my life [PrEP] has taken away the fear of having sex…. Sex has been liberating again, thanks to PrEP.”

According to the researchers, for the most part, the participants’ accounts of PrEP were associated with feelings of empowerment and liberation. However, they were also tempered by their experience of negative attitudes, beliefs and statements from some people in their social and sexual networks. The researchers divided these negative reactions into the following three themes:

  • PrEP-related stigma
  • PrEP and HIV-related stigma
  • PrEP and structural stigma

We now explore these themes.

PrEP-related stigma

The men disclosed that “for many people in their social and sexual networks, PrEP use was equated with having bareback or condomless sex.” The researchers found that the men they interviewed had to manage this assumption “whether or not they were exclusively having condomless sex while on PrEP.”

Some men, because of the stigma associated with PrEP and/or multiple sexual partners, felt it necessary to withhold telling friends and family about their use of PrEP. According to the researchers, these men felt the need to enter “a kind of PrEP closet.” One man made the following comment:

“I hardly told anybody, just because I know my friends would be judgmental—gay or straight. For someone like me who is as out as me, and I’m about as out as anybody, to not admit I’m on PrEP, it’s weird. It’s like there’s still a stigma attached to it, which is totally unfair.”

Some of the men disclosed that they encountered “PrEP-related judgment, stigma or rejection when trying to connect online with prospective sexual partners.” One participant said that he was able to “brush it off” because it was just one person. However, according to the researchers, another participant disclosed more than one experience of “stigma and rejection from friends, which prepared him for subsequent stigmatizing experiences from prospective sexual partners.” This participant made the following statement:

“I just sort of blew it off. I think after my two very early arguments with my best friend and one with a friend who broke the friendship I was prepared for any kind of cursedness, like ‘Oh, you’re on PrEP, I’m not going to sleep with you, because you’re clearly a slut’…and I’m like, ‘you don’t even understand what it’s about.’ That’s fine, whatever.”

PrEP and HIV-related stigma

The researchers found that participants’ use of PrEP caused them to think about, discuss and change or challenge taboos and internalized negative feelings they had toward people living with HIV.

One man said: “I grew up in a time where the notion of unprotected sex was not only stigmatized but people wouldn’t engage sexually with people that were HIV positive, even with condoms.” This man later disclosed that, given this history, his use of PrEP felt “empowering.”

Other participants stated that PrEP allowed them to have “more honest” sex with other men. As one man said: “I know that there is a lot of stigma toward positive guys but when I had sex [with them], I felt like most of the time it was better…. I built good relations, like I have many friends who are undetectable or positive…. I just felt like, you know, we were both honest.”

Well-designed studies have found that HIV-positive people who take treatment (ART) and whose viral load in the blood becomes very low (commonly called “undetectable”) and who maintain this low level of viral load do not pass on HIV during sex. Researchers noted that some men in the present study felt that relying on this form of protection depended on “the actions and adherence of another person.” Researchers said that the men felt that their use of PrEP “allowed them to be in control and do something for themselves to reduce their risk of HIV.”

The researchers found that participants felt that their use of PrEP “lessened feelings of stigma and rejection toward gay men who are HIV positive.”

One man said that he saw his use of PrEP as way of helping to reduce what he referred to as persistent “moral stigma” related to HIV.

Another participant stated: “It kind of made me feel good that I don’t have to ask guys what their status is, and so poz guys don’t have to worry about disclosure or rejection and, you know, all that stigma stuff. And I like the idea that they have a different experience now that there are so many guys on PrEP because some guys would just—like, I don’t ask.”

The researchers noted that more than one PrEP user decided to no longer ask about the HIV status of his potential sex partners. As a result, the researchers made this statement:

“We think it is important to reflect on the public health significance of some men on PrEP saying that they no longer discuss HIV status with sexual partners because of their PrEP use. While this reported change in behaviour may be intended as a form of social progress—aimed at destigmatizing HIV positivity—there may also be potential unintended consequences of this behaviour if it became more widespread. We feel that clinical counselors and PrEP educators should be mindful of this potential change in behaviour as PrEP rollout expands.” The researchers did not provide further details about their concerns.

PrEP and structural stigma

According to the researchers, participants spoke about how PrEP “sometimes exposed broader structural forms of stigma related to PrEP and gay sexuality.” Some of the men saw such stigma as “an insidious structural barrier to broader PrEP awareness and access.”

Related to this, the researchers stated that some men expressed discomfort discussing the following topics with their doctors:

  • their need for PrEP
  • gay sexuality
  • risks related to getting HIV

This discomfort acted as a barrier to accessing PrEP.

The researchers asked participants for recommendations about policy issues regarding PrEP. Below are the themes raised by the men:

  • There needs to be increased education in the community about PrEP.
  • As PrEP is highly effective, it was seen as a cost-effective measure to help prevent HIV.
  • PrEP was seen as giving gay men “equality of access to healthy sex that straight people already have.”

Bear in mind

Although participants reported some degree of negative attitudes and behaviours from some people in their social and sexual networks when they disclosed their use of PrEP, the researchers found that most of the men they interviewed “were reluctant” to assume the identity of a victim or to see PrEP in a negative way because of the stigma they encountered. The researchers noted that “not only were the men able to manage the negative issues associated with PrEP but that stigma rolled off their back.”

Social and societal issues

The researchers found that there was an apparent contradiction in the men’s stories about PrEP. On one hand, disclosing their use of PrEP caused them to experience “stigmatizing reactions within their social and sexual networks.” On the other hand, they described their use of PrEP as helping “to remove stigma, shame and fear related to HIV, sexuality and sex with gay men living with HIV.”

The researchers made the following statement: “We believe that it is essential that these narratives be read with reference to gay men’s political struggle and historical trauma, with an understanding of the evolving policies and discourses that coordinate and regulate gay men’s sexual and social lives. Successfully advocating for broader PrEP access requires that societal and structural stigma surrounding gay sexuality be addressed head on. These accounts of PrEP use help to shed light on broader stigmas and moral panics around sex and sexuality, which may serve to negatively impact both the availability and uptake of PrEP and the health of diverse communities, including, although certainly not limited to, gay men.”

The researchers acknowledged that they interviewed a small group of well-educated white gay men, and so their findings are not likely to apply to other groups. They call for additional research with different communities “who are using or who may benefit from PrEP” to find out about their experiences.

 

By Sean R. Hosein

REFERENCES:

  1. Grace D, Jollimore J, MacPherson P, et al. The pre-exposure prophylaxis (PrEP)-stigma paradox: learning from Canada’s first wave of PrEP users. AIDS Patient Care and STDs. 2018 Jan;32(1):24–30.
  2. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine. 2016; 375:830–9. Available from: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1600693
  3. Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. Journal of the American Medical Association. 2016;316(2):171–81. Available from: http://jama.jamanetwork.com/article.aspx?articleid=2533066
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Man with HIV can train as airline pilot after ban is reversed http://www.eatg.org/news/man-with-hiv-can-train-as-airline-pilot-after-ban-is-reversed/ Thu, 18 Jan 2018 22:25:44 +0000 http://www.eatg.org/?post_type=news&p=7225 Man says he is ‘overwhelmed, shocked, elated and humbled’ by Civil Aviation Authority’s rule change

The Civil Aviation Authority has given a man with HIV permission to seek medical approval to become an airline pilot after reversing its previous ban.

The man, known as Andrew, came forward last year to disclose that the CAA had refused to allow him to start training as a pilot for easyJet because he was HIV positive.

He told BBC Scotland he was “overwhelmed, shocked, elated and humbled” to learn the CAA had now reversed its decision, which it said were due to strict European Aviation Safety Agency (Easa) restrictions linked to certain medical conditions.

Andrew, from Glasgow, had been a keen flyer since he was 15 and gained his private pilot’s licence when he was 17, before he had learned to drive.

After deciding to pursue a career as a professional pilot, he wrote to the CAA using a pseudonym about three years ago to ask what its policy was on allowing HIV-positive people to train.

It then said that if he got a medical certificate, he could train but only to fly with a co-pilot. He passed all easyJet’s assessments and was put on its training programme, but was then told the CAA would not clear him to fly.

That left him very confused, he said. It left him particularly disheartened because that decision undermined his belief that having HIV was not a barrier to having a career.

He told the BBC. “In 2017, someone who is HIV positive and on successful treatment is medically no different to someone who isn’t HIV positive.”

The CAA has now reversed that original ban and confirmed that any applicant who passes their class 1 medical assessment for pilots would be allowed to fly. That includes trainees with insulin-treated diabetes or organ transplants.

Andrew Haines, the authority’s chief executive, said the CAA prided itself on its “progressive” policies towards pilots with medical needs. It was campaigning for updated rules on HIV-positive applicants and was pressing the Easa to investigate a formal rule change “without delay”.

Haines added: “We recognise that this research will take time and we will continue to offer our full support to this work in any way we can. In the meantime, the CAA will issue initial class 1 medical certificates with a restriction to multi-pilot operations to applicants wishing to become commercial pilots, subject to the applicants passing their class 1 medical assessment.”

Patrick Grady, a Scottish National party MP who had taken up Andrew’s case at Westminster, said: “I’m delighted the CAA has seen sense and my constituent will now be granted his commercial pilot’s licence. Nobody should be discriminated against because of their HIV status and this change to CAA rules is long overdue.”

By Severin Carrell

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Tenofovir alafenamide effectively treats HBV, no virologic resistance http://www.eatg.org/news/tenofovir-alafenamide-effectively-treats-hbv-no-virologic-resistance/ Thu, 18 Jan 2018 22:20:01 +0000 http://www.eatg.org/?post_type=news&p=7224 Treatment with tenofovir alafenamide was as effective in suppressing hepatitis B replication as tenofovir disoproxil fumarate with no virologic resistance, according to recently published data on two 96-week trials.

“Tenofovir alafenamide (TAF) is an orally bioavailable prodrug of tenofovir (TFV), a nucleotide analog that inhibits reverse transcription of HIV and HBV,” Kosh Agarwal, MD, from Kings College Hospital, United Kingdom, and colleagues wrote. “TAF was designed to have greater plasma stability than tenofovir disoproxil fumarate (TDF) allowing delivery of the active metabolite, tenofovir diphosphate, to hepatocytes more efficiently than TDF, which must be dosed at relatively high levels to achieve a therapeutic concentration in hepatic cells.”

Study GS-US-320-0110 included 792 patients who were positive for hepatitis B e-antigen and completed 96 weeks of treatment with either TAF 25 mg (n = 530) or TDF 300 mg (n = 262). Study GS-US-320-0108 included 395 patients who were negative for HBeAg and completed 96 weeks of treatment with either TAF (n = 266) or TDF (n = 129). The randomized, double-blind studies were identical in design.

HBeAg-positive study

At the end of 96 weeks, the proportion of patients who received TAF and had HBV DNA less than 29 IU/mL was 73% compared with 75% in those treated with TDF. The adjusted difference of –2.2% (95% CI, –8.3% to 3.9%) was not significant.

The researchers observed treatment failure — or remaining HBV DNA of 29 IU/mL or higher — in 14% of patients treated with TDF and 18% of patients treated with TAF.

The proportion of patients with alanine aminotransferase above the upper limit of normal at baseline who achieved normal ALT at week 96 was 75% in patients who received TAF and 68% in those who received TDF, which researchers reported was significant (8%; 95% CI, 1.2-14.7).

The rate of HBeAg loss between the two groups was 22% in patients who received TAF compared with 18% among those who received TDF. Additionally, the rate of HBeAg seroconversion was 18% in the TAF group compared with 12% in the TDF group. The data indicated neither sets of rates were significantly different.

HBeAg-negative study

At study end, the proportion of patients negative for HBeAg who received TAF and had HBV DNA less than 29 IU/mL was 90% compared with 91% in those treated with TDF. The adjusted difference of –0.6% (95% CI, –7% to 5.8%) was not significant.

The researchers observed treatment failure in 41 patients at week 96, eight of whom had verified HBV DNA of 29 IU/mL or higher between the TAF group (n = 5) and TDF group (n = 3).

The researchers observed treatment failure — or remaining HBV DNA of 29 IU/mL or higher — in 14% of patients treated with TDF and 18% of patients treated with TAF.

The proportion of patients with ALT above the upper limit of normal at baseline who achieved normal ALT at week 96 was 81% in patients who received TAF and 71% in those who received TDF, the difference of which was significant (9.8%; 95% CI, 0.2-19.3).

One HBeAg-negative patient treated with TAF experienced loss of HBV surface antigen and achieved seroconversion to anti-HBs. The researchers observed small but similar mean declines in HBsAg levels in both the TAF group (–0.14) and TDF group (–0.1).

“Consistent with week 48 results, treatment effects between TAF and TDF did not differ statistically in prespecified subgroups including age, race, region, HBV genotype, baseline HBV DNA level and prior oral antiviral treatment status,” the researchers wrote. “Through 96 weeks of double-blind treatment, no resistance development was seen in either treatment group. Further, the superior safety profile of TAF relative to TDF with regard to bone and renal parameters seen at week 48 is confirmed through 96 weeks of double-blind treatment.”

Agarwal K, et al. J Hepatol. 2017;doi:10.1016/j.jhep.2017.11.039.

By Talitha Bennett

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Insulin resistance in HCV may be reversed with DAAs http://www.eatg.org/news/insulin-resistance-in-hcv-may-be-reversed-with-daas/ Thu, 18 Jan 2018 20:30:31 +0000 http://www.eatg.org/?post_type=news&p=7228 Hepatitis C (HCV) is associated with insulin resistance, and elimination of the virus may help re-establish glycemic control in affected patients, according to a prospective case-control study published in the Journal of Gastroenterology and Hepatology.

Investigators enrolled consecutive patients with HCV and advanced liver fibrosis who were being considered for direct-acting antiviral (DAA) medication (N=133). Researchers evaluated patients treated with DAAs (n=68) and untreated patients (n=65). At baseline, all patients were free of insulin resistance and type 2 diabetes.

At baseline, insulin resistance was 52.3% and 53.8% in treated and untreated patients, respectively. Various DAA treatments were used, including simeprevir + sofosbuvir (43%), ombitasvir/paritaprevir/ritonavir + dasabuvir (45%), and ledipasvir/sofosbuvi (12%). All patients had cleared their HCV at 3-month follow-up, with 95.6% of patients achieving a sustained virologic response.

Approximately 76.5% of patients who achieved a sustained virologic response experienced improvements in insulin resistance. There was a significant 2.42±1.85 point reduction in insulin resistance as assessed by the homeostatic model assessment insulin resistance (HOMA-IR) test (P <.001). Eradication of HCV was also associated with improved insulin sensitivity and decreases in serum blood glucose and insulin. Patients presenting with a high degree of fibrosis at baseline, however, maintained some level of insulin resistance following treatment (P <.04).

The relatively small number of patients included in this analysis prohibits establishing conclusive evidence on the true benefits associated of HCV treatment on reducing insulin resistance.

In addition to the main findings, the investigators also found that the body mass index (BMI) of patients remained unchanged following treatment, suggesting “that the changes in insulin resistance were independent of BMI [and] further supporting the role of HCV-genotype 1 in the development of insulin resistance.”

By Brandon May

Reference

Adinolfi LE, Nevola R, Guerrera B, et al. HCV clearance by direct-acting antiviral treatments reverses insulin resistance in chronic hepatitis C patients [published online December 11, 2017]. J Gastroenterol Hepatol. doi:10.1111/jgh.14067

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Elbasvir/grazoprevir plus ribavirin improves SVR in certain HCV genotypes http://www.eatg.org/news/elbasvirgrazoprevir-plus-ribavirin-improves-svr-in-certain-hcv-genotypes/ Thu, 18 Jan 2018 20:29:49 +0000 http://www.eatg.org/?post_type=news&p=7230 Elbasvir/grazoprevir (EBR/GZR) with or without ribavirin (RBV) appears to be tolerable and effective for achieving a sustained virologic response (SVR) at 12 weeks in certain genotype hepatitis C (HCV) infections, according to study findings published in the Journal of Viral Hepatitis.

In this randomized, open-label trial consisting of treatment-naive, noncirrhotic patients with HCV genotype 2, 4, 5, or 6 infection, investigators assessed the effect of EBR/GZR with or without RBV on SVR. Virologic response at 12 weeks after treatment made up the primary endpoint for this study. In addition, investigators evaluated the treatment’s associated adverse outcomes, including fatigue, headache, asthenia, nausea, and cough.

Those with the HCV genotype 2 infection were randomly assigned to receive GZR 100 mg in addition to RBV ± elbasvir 50 mg for 12 weeks. Participants with HCV genotype 4, 5, or 6 infection received EBR/GZR ± ribavirin for the same period. A SVR response at 12 months was achieved by 80% of participants with genotype 2 infection who were assigned to EBR/GZR plus RBV vs 73% of genotype 2 patients assigned to GZR and RBV.

Rates of SVR were fairly high among patients with HCV genotype 4 infection randomly assigned to EBR/GZR with and without RBV (100% and 90%, respectively). Adding RBV to the EBR/GZR combination therapy improved the 12-week SVR among patients with genotype 5 infection (EBR/GZR [25%] vs EBR/GZR plus RBV [100%]). Approximately 75% of patients with genotype 6 HCV infection in both the EBR/GZR and EBR/GZR plus RBV groups achieved a SVR at follow-up. In addition, patients receiving RBV experienced more frequent adverse events than patients receiving EBR/GZR.

The small number of patients with HCV genotypes 5 and 6 in this analysis limits the ability to draw firm conclusions on treatment “of people infected with these genotypes and the impact [of] resistance associated substitutions.”

By Brandon May

Reference

Brown A, Hézode C, Zuckerman E, et al; for the C-SCAPE Study Investigators. Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with HCV genotype 2, 4, 5, or 6 infection: the C-SCAPE study [published online November 20, 2017]. J Viral Hepat. doi: 10.1111/jvh.12801

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Smoking reduces survival after liver cancer diagnosis for people with viral hepatitis http://www.eatg.org/news/smoking-reduces-survival-after-liver-cancer-diagnosis-for-people-with-viral-hepatitis/ Thu, 18 Jan 2018 20:11:38 +0000 http://www.eatg.org/?post_type=news&p=7222

People with viral hepatitis who smoked were three times more likely to die after being diagnosed with liver cancer (hepatocellular carcinoma, HCC), according to a study of Swiss patients published in Liver International.

Whereas non-smokers lived for a median of 3.2 years after diagnosis, smokers died after a median of 18 months. Smoking had a similar impact on survival in those who did not receive curative treatment in the form of liver resection (surgery), liver transplantation or ablation (use of heat to destroy tumours in the liver).

Smoking has been found to increase the risk of developing liver cancer in some, but not all studies, and to increase the risk of liver cancer in some studies of people with viral hepatitis.

To look at the effect of continuing to smoke after a diagnosis of primary liver cancer (HCC) Swiss researchers analysed survival in 238 people with at least 12 months of follow-up after diagnosis of HCC. Sixty-four reported smoking at the time of inclusion in the cohort study. Smokers were followed for a median of 489 days and non-smokers for 1170 (p = 0.002), the difference reflecting the poorer survival in smokers.

HCC developed at a younger age in smokers (59 vs 66 years, p < 0.001).

There was no significant difference between smokers and non-smokers in the stage of liver cancer whether measured by Child-Pugh grade or BCLC (Barcelona Clinic Liver Cancer) system, nor in any markers of liver damage with the exception of platelet counts and INR (international normalised ratio) scores. Smokers showed some evidence of greater liver injury. They had lower platelet counts and slightly higher INR scores. (Smokers usually have higher platelet counts than non-smokers.)

There was no difference between smokers and non-smokers in the type of treatment they received.

HCC attributable to viral hepatitis (B or C) or alcohol was more common in smokers.

A multivariate analysis which controlled for other risk factors showed that smoking increased the risk of death in people with viral hepatitis diagnosed with HCC (HR 2.41, 95% CI 1.28-4.41, p = 0.007) but not in people with liver cancer attributable to other causes. A more advanced stage of HCC at diagnosis also increased the risk of death (HR 2.73, 95% CI 1.93-3.85, p < 0.001).

Smoking is known to increase liver fibrosis in people with hepatitis C and might also directly influence HCC progression after diagnosis. Poorer fitness or less compliance with medical treatment or advice might also affect survival, the investigators suggest. They say that it is not possible to tell from their cohort whether the effect of smoking was a consequence of smoking intensity – how many cigarettes a day – or duration (persistence in smoking after diagnosis).

“Based on these findings, smoking cessation should be considered for incorporation into the disease management for patients with HBV or HCV [with HCC],” the authors conclude. They point out that around 80% of HCC cases worldwide are probably attributable to viral hepatitis.

By Keith Alcorn

Reference

Kolly P et al. Effect of smoking on survival of patients with hepatocellular carcinoma. Liver International 37: 1682-1687, 2017.

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Injection drug users benefit from hepatitis C treatment http://www.eatg.org/news/injection-drug-users-benefit-from-hepatitis-c-treatment/ Thu, 18 Jan 2018 19:51:23 +0000 http://www.eatg.org/?post_type=news&p=7227 Since the emergence of costly direct-acting antiviral drugs, much controversy has surrounded the issue of which patients with hepatitis C virus (HCV) should receive treatment. Due to the high costs of these drugs, some payers only granted access to patients with late-stage cirrhosis.

The opioid epidemic and related boom in injection drug use has resulted in even more questions: should people who inject drugs (PWID) receive HCV treatment and if these patients do receive payer approval, will they respond to therapy?

A new study published by the Lancet Gastroenterology & Hepatology suggests that a majority of PWID can achieve a sustained viral response at 12 weeks.

Included in the analysis were 103 patients with HCV genotypes 1 to 4 who reported using injection drugs in the previous 6 months. Patients were treated with daily sofosbuvir-velpatasvir for 12 weeks.

At baseline, approximately three-quarters of patients used injection drugs within the previous month and 60% of patients received opioid substitution treatment.

The authors found that 99 out of 100 patients who finished treatment achieved a response.

Approximately 94% of patients achieved a sustained virologic response at 12 weeks, which was the primary efficacy endpoint of the trial, according to the study. The authors found that there were no virological failures.

Injection drug use prior to and during HCV treatment was not observed to impact virologic response, according to the study.

Less than half of patients experienced a treatment-related adverse event and only 7% experienced a serious adverse event. There was also a single case of HCV re-infection observed, according to the authors.

Current guidelines suggest that PWID should receive treatment for HCV, but several factors—including stigma—may prevent physicians from prescribing the drugs.

“Stigma … has resulted in insurance restrictions and reluctance from providers to offer appropriate medical therapy,” the authors wrote.

The authors note that physicians should offer HCV therapy to PWID and that recent injection drug use should not justify withholding drug reimbursement, according to the study.

These findings suggest that PWID with HCV “can and should be treated with direct-acting antivirals,” the authors concluded.

By Laurie Toich

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U=U laggards draw fire from the community http://www.eatg.org/news/uu-laggards-draw-fire-from-the-community/ Wed, 17 Jan 2018 22:59:19 +0000 http://www.eatg.org/?post_type=news&p=7212 The global U=U picture is good, but community activists are stepping up the heat on organizations which have been slow to embrace it. Today the spotlight is on Greater than AIDS, GNP+ and in Canada, the Ontario AIDS Network. Bob Leahy reports.

Read the full publication here.

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Timothy Ray Brown, cured of HIV, rallies public to support research funding http://www.eatg.org/news/timothy-ray-brown-cured-of-hiv-rallies-public-to-support-research-funding/ Wed, 17 Jan 2018 22:55:17 +0000 http://www.eatg.org/?post_type=news&p=7216 New Rochelle, NY, January 17, 2018—In the 10th anniversary year since a bone marrow stem cell transplant cured Timothy Ray Brown of his HIV infection, despite disappointment over decreasing public desire to find a cure for HIV, Timothy Ray Brown remains optimistic that the scientific and medical communities can and will achieve this if properly funded. He describes his most recent activities and the basis for his pessimism and optimism in the article “Timothy Ray Brown’s Continuing Activism Toward Curing HIV,” published in the latest HIV Cure Research Issue of AIDS Research and Human Retroviruses, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the AIDS Research and Human Retroviruses website.

Throughout his “10 Cure Birthday” year’s busy schedule of activities, Timothy Ray Brown “learned a few things last year that I found disappointing…I participated in two HIV cure seminars…The responses from many [participants] surprised me. Perhaps I misinterpreted this but I would say most of them indicated that they were afraid of HIV being cured. This is mostly due to the fear of how it would worsen their lives, that they would stand to lose all or most of the benefits they have today.”

“The development of drugs to treat HIV infection has saved countless lives but led to complacency about this horrible virus,” says Thomas Hope, PhD, Editor-in-Chief of AIDS Research and Human Retroviruses and Professor of Cell and Molecular Biology at Northwestern University, Feinberg School of Medicine (Chicago, IL). “In this update of his travels as an advocate of HIV cure research, Timothy Ray Brown reminds us that we still need to advocate for funding and educate the public about the important impact that a functional cure for HIV would have on society while understanding the complex ways that a cure would impact people living with AIDS. His insights as the first person cured of HIV are fascinating.”

About the Journal

AIDS Research and Human Retroviruses, published monthly online with open access options and in print, presents papers, reviews, and case studies documenting the latest developments and research advances in the molecular biology of HIV and SIV and innovative approaches to HIV vaccine and therapeutic drug research, including the development of antiretroviral agents and immune-restorative therapies. Content also explores the molecular and cellular basis of HIV pathogenesis and HIV/HTLV epidemiology. The Journal features rapid publication of emerging sequence information, reports on clinical trials of emerging HIV therapies, and images in HIV research. Tables of content and a sample issue may be viewed on the AIDS Research and Human Retroviruses website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including AIDS Patient Care and STDs, Viral Immunology, and Journal of Interferon and Cytokine Research. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

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WHO leadership meets with TB civil society to strengthen engagement in accelerating the End TB response http://www.eatg.org/news/who-leadership-meets-with-tb-civil-society-to-strengthen-engagement-in-accelerating-the-end-tb-response/ Wed, 17 Jan 2018 22:50:24 +0000 http://www.eatg.org/?post_type=news&p=7219 17 January 2018 | Geneva: Civil society representatives met with WHO leadership in Geneva, on 15-16 January 2018, with the aim of strengthening collaboration to end TB. WHO Director-General Dr Tedros Adhanom Ghebreyesus and Dr Tereza Kasaeva, Director of the WHO Global TB Programme, opened the meeting, and Dr Soumya Swaminathan, Deputy Director-General, Dr Ren Minghui, Assistant Director General for the Cluster for Communicable Diseases, Dr Berhard Schwartlander, Chef de Cabinet, and Dr Lucica Ditiu, Executive Director of the Stop TB Partnership all expressed support for a much closer working relationship.

“It is inspiring to meet with TB civil society representatives at WHO,” said  WHO Director-General Dr Tedros Adhanom Ghebreyesus. “We all need to work as one if we are to end TB. I am solidly committed to this cause with my strong leadership team and in collaboration with the Stop TB Partnership.”

The effort to strengthen civil society engagement comes on the heels of increased political attention, with the First WHO Global Ministerial Conference on Ending TB held in Moscow last November, as well as other high level meetings which highlighted TB in their communiques including the BRICS and G20.  2018 is seen as a critical year with the upcoming UN General Assembly High Level Meeting (UNHLM) on TB, which will bring together Heads of State.

During the Geneva meeting, Ms Blessi Kumar from the Global Coalition of TB Activists stated, “Never before in the history of WHO has meaningful engagement with civil society and communities been taken so seriously. I feel a lot of hope for the End TB response moving forward and would like to thank Dr Tedros and Dr Tereza for their openness to listen and engage. This will be critical not only in the lead up to the UNHLM on TB, but also beyond.”

Building on a decade of collaboration of WHO with TB civil society, discussions revolved around the next phase of effective engagement in order to accelerate efforts to end TB, as well as in preparations towards the UNHLM on TB. Key asks were formulated for the WHO Director-General, including support in ensuring meaningful engagement of civil society at regional and country levels through WHO Regional and Country Offices, and through interactions with Ministers of Health.

“Civil Society engagement is invaluable to efforts to end TB and reach the Sustainable Development Goals as a whole,” said Dr Tereza Kasaeva, Director of the WHO Global TB Programme. “Their voice and actions will enable no one to be left behind. Together we are stronger.”

Dr Lucica Ditiu, Executive Director of the Stop TB Partnership added, “We have 12 years to end TB and only together can we achieve this. At Stop TB Partnership, we are thrilled with the new WHO leadership’s strategic vision to work together, hand in hand, with us and civil society and communities to end TB. We are committed to work as ONE team to achieve our objective and this is an inspirational way to start the new year!”

This meeting was Dr Tedros’ third major interaction with TB civil society as WHO Director-General. He met with civil society, in advance of the Ministerial Conference on Ending TB on 16 November. This was followed by a teleconference with civil society representatives in late December. The Geneva meeting is only the first of a series of meetings planned this year.

Snapshot: Voices of Meeting Participants

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Long-acting injectable ARVs are convenient and private, study participants report http://www.eatg.org/news/long-acting-injectable-arvs-are-convenient-and-private-study-participants-report/ Wed, 17 Jan 2018 21:52:03 +0000 http://www.eatg.org/?post_type=news&p=7211

HIV-positive people who took injectable cabotegravir + rilpivirine every four or eight weeks as antiretroviral therapy found it more convenient and discreet than daily pills, also feeling that it eliminated a “daily reminder of living with HIV”, Deanna Kerrigan and colleagues report in PLOS One.

Similarly, HIV-negative men who took injectable cabotegravir every 12 weeks as pre-exposure prophylaxis (PrEP) felt that it was probably more convenient and easier to adhere to than daily pills, according to a study from the same research team published in AIDS & Behavior.

Healthcare providers were also supportive, but did point out that the clinical management of long-acting injectable antiretrovirals (ARVs) is more complex. They noted that injectables will not necessarily eliminate the challenge of adherence, with regular attendance at clinic visits more crucial than ever.

Both studies involved in-depth interviews with subsets of people who had taken part in phase II clinical trials, as well as with healthcare providers at trial sites.

The LATTE-2 trial provided cabotegravir + rilpivirine to HIV-positive people who had not previously taken HIV treatment before, in the United States and Spain. Injections occurred every four or eight weeks, depending on which study arm a person was randomised to. For the follow-up qualitative study, 27 study participants and 12 healthcare providers were interviewed.

The ÉCLAIR trial provided cabotegravir to HIV-negative men, as PrEP, in the United States. Participants had injections every 12 weeks, although it has since become clear that an eight-week schedule is more likely to be effective. For the qualitative study, 26 participants and four healthcare providers were interviewed.

In both studies, most but not all of the trial participants interviewed were gay men in their thirties. As people who had volunteered to take part in these studies, they may be more motivated and enthusiastic about injections than other people who need ARVs. Also whereas by definition the HIV-positive participants all needed HIV treatment, most of the HIV-negative participants did not feel that they were at high enough risk to need to take PrEP for themselves.

Most trial participants had had some side-effects from the injections, typically soreness and minor bruising at the injection site for a day or two. A minority had more severe reactions such as fever or impaired mobility. Nonetheless, most felt that the side-effects were “worth it”, as this man taking cabotegravir + rilpivirine for HIV treatment explained:

“One day is nothing… It’s as if you have a day with a headache. You take ibuprofen and that’s it. You put up with it. It’s temporary.”

Injections were felt to be more convenient and easier to adhere to than daily pills by both sets of participants. Especially among those living with HIV, injections were felt to be more private, as other people would not inadvertently see their medication.

“It seems to me that it’s much better because you simply don’t have to worry about anything. If you go on a trip, you don’t have to bring your pills or take anything at all along. You follow your ‘normal life.’ You come once a month. You get the shot and it’s over. You don’t have to be thinking everyday… oh I forgot to take the pill. Or… when did I take it last… You just don’t worry about anything. In reality, taking the pill everyday keeps it [HIV] present… and the shot is just once a month… You remember it when you come in and the rest of the time you can basically forget it.”

Nonetheless, a few participants did express concern about the number of clinic visits required. Friends, family and work colleagues could ask why the person needed to see the doctor so often, potentially leading to unwanted disclosure of HIV status.

Participants agreed that the intramuscular injections (in the buttocks) needed to be provided by a skilled professional, such as a doctor or nurse. A number of possible clinical settings were suggested for providing the injections, but self-injection was not felt to be realistic.

Gay men taking part in the PrEP trial often felt that the injection could give ‘peace of mind’, especially given unanticipated risks.

“I’m thinking why not do injectable PrEP because there could be that one night where you’re not even planning for that, you’re like, oh wait, I have to take pills for a week before I even consider doing this. Because for men who have sex with men, being spontaneous is there. The hookup culture is so prevalent.”

When asked who are the ‘right people’ to use injectables – rather than daily pills – respondents often referred to people who find adherence challenging. Mention was made of people with unstable lives, homeless individuals, substance users and younger people. Potential users must also not have an aversion to needles.

But most of the people living with HIV said that they would recommend injectables to ‘anyone’ living with HIV. Several said that their friends were jealous when they learned of how they were taking their medication.

“90% of the people will prefer this method.”

However, the healthcare providers who were interviewed suggested that injections may not be right for everyone, with the choice of medication best decided on a case by case basis. While people who are less likely to adhere to daily pills might theoretically be good candidates for injectables, they noted that people still need to show up for appointments.

“My concern with injections is this: when you have someone who’s just not compliant. If they’re not compliant and they miss two or three oral doses, it’s not the end of the world. If you’re not compliant with every eight weeks, that could be an issue. So you’ve got to get people who understand the importance of adhering.”

One older man living with HIV noted that as he needed to take several other oral medications in addition to his HIV treatment, he was happy to stick with the pills.

Clinicians also noted that the clinical management of injectables was more complex than with daily pills. Patients need to begin with oral drugs, then switch to injectables, a process which needs to be actively managed. Injectables cannot be discontinued quickly in the event of adverse reaction. Moreover, cabotegravir persists in the body for a long time after discontinuation, potentially creating problems in relation to drug resistance.

To conclude, both injectable HIV treatment and injectable PrEP were highly acceptable and feasible for study participants, with the potential to allow for better adherence.

By Roger Pebody

References

Kerrigan D et al. Experiences with long acting injectable ART: A qualitative study among PLHIV participating in a Phase II study of cabotegravir + rilpivirine (LATTE2) in the United States and Spain. PLOS ONE 13(1): e0190487, 2018. (Full text freely available.)

Kerrigan D et al. Expanding the Menu of HIV Prevention Options: A Qualitative Study of Experiences with Long-Acting Injectable Cabotegravir as PrEP in the Context of a Phase II Trial in the United States. AIDS & Behavior, online ahead of print, 2017. (Abstract.)

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First chronic hepatitis B patient dosed in China in a Phase 1 trial of T101 (Transgene’s TG1050 technology) http://www.eatg.org/news/first-chronic-hepatitis-b-patient-dosed-in-china-in-a-phase-1-trial-of-t101-transgenes-tg1050-technology/ Wed, 17 Jan 2018 21:48:09 +0000 http://www.eatg.org/?post_type=news&p=7215 STRASBOURG, France, January 17, 2018: Transgene (Paris:TNG) (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies, announces that the first patient has been dosed in a Phase 1 clinical trial in China, evaluating T101, a therapeutic vaccine based on Transgene’s immunotherapy technology for the treatment of chronic hepatitis B virus (HBV) infection. This product is a viral vector expressing the same suite of patented HBV antigens as in TG1050, currently in clinical development in Europe and North America.

T101 is being developed in China through Transgene’s joint-venture with Tasly Pharmaceutical Group Co, Ltd. This Chinese corporation was created in 2010 to develop biotechnology products, including Transgene products, in China. This company is jointly owned (50%/50%) with Tasly Pharmaceutical Group Co, Ltd, which is based in Tianjin, China.

The Phase 1 trial is a randomized, single-center, double-blind, placebo-controlled study evaluating T101 in patients who are currently being treated for chronic HBV infection with standard-of-care antiviral therapy. The primary objective of this study is to validate the tolerability of T101 administered in single and multiple ascending doses. The trial will also evaluate the immunogenicity of the therapeutic vaccine in a patient population whose characteristics differ from European and North American patients (e.g. different modes of contamination, different population haplotypes), and who can be infected with different genotypes of the virus. This trial will include up to 36 patients. The first data readout from the study is expected at the beginning of 2019.

Currently available antiviral treatments can control the chronic hepatitis B but not cure the disease. Even under chronic treatment, patients still have a high probability to develop cirrhosis and liver cancer. In China, 500,000 patients could benefit from a better therapeutic option.

T101 is a targeted immunotherapy candidate for the treatment of chronic hepatitis B, based on a viral vector expressing three HBV antigens. It has been designed by Transgene’s infectious diseases research team, based on the technology of Transgene’s therapeutic vaccine TG1050.

TG1050 is currently being evaluated by Transgene in a Phase 1/1b trial with TG1050 in chronic HBV patients treated with standard-of-care antiviral therapies in Europe and Canada. The first results from this clinical trial have confirmed the good tolerability profile of TG1050. This study has also demonstrated the dose-related immunogenicity of this novel therapeutic vaccine following a single administration to patients with chronic hepatitis B receiving standard antiviral therapy. Additional data on patients receiving multiple doses of TG1050 are expected to be presented at a major international conference dedicated to liver diseases in H1 2018.

About Transgene

Transgene (Euronext: TNG), part of Institut Mérieux, is a publicly traded French biotechnology company focused on designing and developing targeted immunotherapies for the treatment of cancer and infectious diseases. Transgene’s programs utilize viral vector technology with the goal of indirectly or directly killing infected or cancerous cells. The Company’s lead clinical-stage programs are: TG4010, a therapeutic vaccine against non-small cell lung cancer, Pexa-Vec, an oncolytic virus against liver cancer, and TG4001, a therapeutic vaccine against HPV-positive head and neck cancers. The Company has several other programs in clinical development, including TG1050 (chronic hepatitis B) and TG6002 (solid tumors).
Transgene is based in Strasbourg, France, and has additional operations in Lyon, as well as a joint venture in China. Additional information about Transgene is available at www.transgene.fr.

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Fresh approach to TB vaccine offers better protection http://www.eatg.org/news/fresh-approach-to-tb-vaccine-offers-better-protection/ Wed, 17 Jan 2018 21:02:28 +0000 http://www.eatg.org/?post_type=news&p=7218 New vaccine completely protected 41 percent of nonhuman primates; standard vaccine protected none

A unique platform that resulted in a promising HIV vaccine has also led to a new, highly effective vaccine against tuberculosis that is moving toward testing in humans.

The new vaccine completely protected 41 percent and reduced overall TB disease by 68 percent in vaccinated rhesus macaques, according to a study published in Nature Medicine. In contrast, there was no measurable protection in the rhesus macaques — a monkey species that is closely related to humans — treated with today’s standard TB vaccine, the Bacillus Calmette–Guérin vaccine.

“With more than 1.7 million people dying globally from TB each year and the rise of strains that are resistant to drug treatment, we need a better way to prevent this disease,” said principal investigator Louis Picker, M.D., who is the associate director of the OHSU Vaccine and Gene Therapy Institute and a professor of pathology, and molecular microbiology and immunology in the OHSU School of Medicine.

“Because rhesus monkeys are significantly more susceptible to TB than humans and, given how effective our new TB vaccine has been in these monkeys, we feel that the human version of our vaccine could have the potential to be even more effective in protecting humans,” Picker said.

TB disease is caused by the bacteria Mycobacterium tuberculosis, is spread through the air, and can lead to violent cough attacks involving spitting up blood. Most people infected with TB don’t even know it; only 5 to 10 percent show symptoms. A vaccine already exists, but it largely protects children and its efficacy varies widely.

Picker and colleagues have taken a different approach to vaccination. They use a weakened form of a common herpes virus — cytomegalovirus, or CMV — which infects most people without causing disease. In collaboration with the TB nonprofit Aeras, they wove tiny bits of a disease-causing pathogen into the CMV. This re-engineered CMV creates and maintains a high state of immunity against the pathogen in vaccinated monkeys. This approach has the potential to work better than standard vaccines for aggressive pathogens that infect quickly, overrun a person’s immune response or can hide from the immune system.

The new TB vaccine reduced overall disease by 68 percent in vaccinated monkeys. About 41 percent of vaccinated monkeys were completely protected from TB, while 30 percent had less severe disease than unvaccinated monkeys, and another 30 percent showed no benefit from the vaccine. This level of protection has never been seen before in rhesus macaques with the standard TB vaccine.

Next, Picker and colleagues will work to better define the biological mechanisms by which their new TB vaccine works. They will also work with Vir Biotechnology, Inc. of San Francisco, which has licensed aspects of their CMV-based vaccine approach, to expand testing with plans to start a human clinical trial in 2020.

Vir Biotechnology plans to manufacture the HIV/AIDS vaccine, which is also made with CMV, in 2018 and a human clinical trial is slated for 2019.

The success of both vaccines thus far in stringent monkey models has led Picker and his colleagues to believe their CMV-based approach to making vaccines has the potential to be engineered to tackle a variety of infectious diseases.

This research was supported by Aeras, the Bill & Melinda Gates Foundation (grant OPP1087783), and the National Institutes of Health (grants U19 AI106761, P51 OD011092 and U42 OD010426).

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We found ways to shorten the turnaround time for diagnosing babies with HIV http://www.eatg.org/news/we-found-ways-to-shorten-the-turnaround-time-for-diagnosing-babies-with-hiv/ Wed, 17 Jan 2018 20:41:44 +0000 http://www.eatg.org/?post_type=news&p=7214 They say timing is everything. And in sub-Saharan Africa, where roughly a third of untreated HIV infected babies die before they reach the age of one, a timely diagnosis is everything.

According to the latest UNAIDS data, 150 000 children are infected with HIV in sub-Saharan Africa, annually. Due to the high number of children dying, diagnosing babies with HIV as early as possible is critical.

Public health officials have been grappling with this for many years. How can they reduce the time it takes to get newborns’ blood samples to the diagnostic lab and the test results back? This matters because it determines how soon babies can start medical treatment. The average turnaround time in sub-Saharan Africa often range from one to three months.

In general, shorter turnaround times can be achieved by improving the clinic-to-lab supply chain. This can happen through increasing the number of vehicles equipped to transport samples, hiring enough drivers, training enough medical personnel, buying the right type of diagnostic equipment, and improving communication systems.

African countries like Malawi and Nigeria have done this, with impressive results.

But as we show in our new study improving the day-to-day operations of clinic-to-lab supply chains is simply not enough. Sometimes the opportunities lie in the structure of the supply chain itself.

We came to this conclusion after evaluating the early infant diagnosis network in Mozambique. It’s one of many sub-Saharan African nations struggling to improve its turnaround time for HIV testing.

We examined tens of thousands of cases in Mozambique right down to the original time stamps on samples and the return dates of test results. Then we developed a tool to streamline this supply chain system. We found that some simple changes could improve the turnaround time and increase the number of infants starting treatment.

An inefficient system

One of the biggest barriers to faster test turnaround times in Mozambique has to do with the network structure of laboratories and clinics. There are about 400 clinics in the country. These are assigned to laboratories based on governmental administrative districts. But these boundaries are drawn for political reasons instead of public health reasons.

As a result one administrative district may be densely populated while another is sparsely populated. And this means that the workload at the various diagnostic laboratories differs according to the size of their surrounding populations.

If too many clinics send their samples to the same lab, they become congested and results are delayed. But if too few clinics send their samples to a given lab, the technicians have to wait longer to gather enough samples to justify conducting tests. This is because it costs just as much to test 100 samples as it does one sample – and the materials are expensive.

Changing the system

For our study we developed two models which captured the operational, medical, and behavioural factors affecting an early infant diagnosis network’s effectiveness.

In the first model we re-assigned clinics to labs to maximize the number of infants who start treatment, by minimizing the turnaround time of results.

It showed us two important things. Firstly, a relatively minor modification reassigning some clinics to different labs could decrease the average sample turnaround time by 11% compared with the current system.

Secondly, this increased the number of infected infants starting treatment by about 4%.

But we took our modelling one step further. In our second model we wanted to determine if relocating the existing diagnostic machinery between labs could have an even larger public health impact.

What we found was that consolidating all diagnostic capacity in one centralised lab is optimal. Based on our study we predict that consolidation could decrease the average turnaround times by an estimated 22% and increase the number of infected babies initiating treatment by 7%.

This result has implications, as consolidating diagnostic laboratories has been a much-debated issue in the field of public health in sub-Saharan Africa.

The bigger picture

Improving turnaround times between the diagnostic lab and the clinic and speeding up the initiation date for HIV positive babies to start treatment boils down to using operations management to improve global health.

By shaving precious days, weeks and even months off diagnostic turnaround times, infants infected with HIV are able to get treatment quicker.

Whether it’s reassigning clinics among the existing labs, or optimally reallocating the diagnostic capacity to a centralised lab, improvements need to be made because timing truly is everything.

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Global summit on IP and access discusses impact of TRIPS-Plus measures on public health http://www.eatg.org/news/global-summit-on-ip-and-access-discusses-impact-of-trips-plus-measures-on-public-health/ Wed, 17 Jan 2018 19:57:31 +0000 http://www.eatg.org/?post_type=news&p=7217 A network of civil society organisations chose the birthplace of the World Trade Organization, Marrakesh, to hold a global summit on intellectual property and access to medicines this week. Part of the summit focused on stringent IP measures in free trade agreements in particular with the European Union, introducing patent term extension and data exclusivity periods.

The Global Summit on Intellectual Property & Access to Medicines: Pathways to Access is taking place from 15-17 January in Marrakesh, Morocco. At the same time as the agreement to establish the World Trade Organization, the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) was adopted by all WTO members in 1994.

The summit was organised by the International Treatment Preparedness Coalition (ITPC), and is meant to bring together community representatives, governments, civil society, academics, experts and international agencies to look at the impact of international trade rules on public health, and highlight the role of non-governmental organisations and patients in the implementation of TRIPS flexibilities.

A number of panels were organised around the themes of the role of patent examination to prevent bad patents; making compulsory licences (CLs) routine; understanding and resisting TRIPS-plus measures; how least-developed countries can make effective use of the transition periods; local production and technology transfer; possibilities and challenges of pro-health patent law reform in developing countries; and challenging unmerited patents.

The panel on resisting TRIPS-plus measures described efforts to fight measures that go beyond the TRIPS minimum requirements.

EU Seeking TRIPS-Plus Measures in Morocco

Mohammed Said Saadi, economist and a former minister in Morocco, said since the 1980s there has been a clear regression of human rights in the context of international trade, due to neo-liberal policies. The Southern and Eastern Mediterranean region is the object of fierce competition between the United States and the European Union, both coveting the regional market, he said.

The United States scored on the pharmaceutical front, and advanced its interests through free trade agreements with Jordan and Morocco, he said.

According to Saadi, the EU is trying to impose a new trade agreement aligned with TRIPS-plus measures that Jordan and Morocco have already accepted through their free trade agreement with the US.

The ongoing Deep and Comprehensive Free Trade Area (DCFTA) discussions between the EU and Morocco are introducing TRIPS-plus measures, he said, underlining the secrecy of the negotiations.

There have been very few studies on the impact of TRIPS implementation in Morocco and in Jordan, he said, adding that he only found one impact study. Oxfam published a briefing paper [pdf] titled, “All costs, no benefits: How TRIPS-plus intellectual property rules in the US-Jordan FTAs affect access to medicines,” in 2007.

According to the study, medicines prices in Jordan have increased 20 percent since 2001, and “higher medicine prices are now threatening the financial sustainability of government public health programmes.”

Saadi said data exclusivity has delayed generic competition for 79 percent of medicines newly launched, and almost no foreign direct investment was done by drug companies into Jordan.

EU-Mercosur, TRIPS-Plus Measures, Assessment

Daniel Pinto, counsellor, Intellectual Property Division, Brazilian Ministry of Foreign Relations, talked about the ongoing Mercosur-EU trade negotiations. The current trade agreement with the EU is being negotiated with the four founding members of Mercosur (Argentina, Brazil, Paraguay, and Uruguay), according to the EU website.

Pinto underlined the reliance of Mercosur countries on exports of agricultural products, which makes the agreement with the EU very important to access the EU market. Mercosur, however, is not as consolidated as the EU, the four countries do not have the same interests, legal systems are not always harmonised, and they also do not have much experience in joint negotiations, he said. Thus negotiations go into two tracks, the first is negotiating with the EU, and the other is building confidence among Mercosur countries, he added.

In the Mercosur discussions, Pinto noted that the EU requested that in case of administrative delay by drug regulatory authorities to bring a patented medicine on the market, the patent term would be extended accordingly. He said in that case an administrative solution should be found to address the issue, not extending the patent term, as the two issues are unrelated.

The EU follows its argument according to which over 42 percent of the total economic activity in the EU is generated by intellectual property-intensive industries, he said. However, the impact of the proposed TRIPS-plus measures on countries should also be taken into consideration, he added.

He cited a 2017 Mercosur-EU Free Trade Agreement impact analysis [pdf] of TRIPS-plus measures proposed by the EU on public purchases and domestic production of HIV and hepatitis C medicines in Brazil. The study was co-authored by Gabriela  Costa  Chaves, Sergio Arouca, Walter Britto Gaspar of the Oswaldo Cruz Foundation (ENSP/Fiocruz), and Marcela Fogaça Vieira, consultant for the Shuttleworth Foundation.

The analysis, which was explained by the authors in an Intellectual Property Watch Inside Views article (IPW, Public Health, 1 December 2017), found that if a 5-year data exclusivity in patent term extension is agreed upon, it would translate in an additional expenditure of US$ 1.2 billion from 2015 to 2050 for HIV medicines, and for hepatitis C medicines, an additional expenditure of US$14.5 billion from 2016 to 2051, he said.

Intellectual property is not a bargaining chip, Pinto said, and added that the lack of clarity about what is at stake in IP jeopardises efforts to preserve policy space. He called for civil society to continue to raise awareness and apply political pressure, for academia and researchers to provide impact studies based on hard facts, and for negotiators to be mindful of their responsibility toward present and future generations.

Once TRIPS flexibilities are given away, the cost of recovering them is huge, he said in his presentation.

Fogaça Vieira said the IP chapter of the EU-Mercosur FTA would affect parallel imports, provide an extension of the patent term, and introduce data exclusivity.

The impact of TRIPS-plus measures in Brazil would affect hepatitis C medicines more than they would antiretrovirals, because Brazil has put in place some policies to reduce the impact of TRIPS-plus measures on those medicines, which is not the case for hepatitis C, she explained.

She suggested that more impact studies be done on public health and human rights impacts of TRIPS-plus measures proposed in FTAs, and that the negotiations should be more transparent.

Lorena di Giano of Fundación Grupo Efecto Positivo (FGEP) in Argentina, a Mercosur country, said Argentina has no data exclusivity provision in its law. The country conducted a IP impact assessment study performed on 17 antiretroviral drugs procured by the National Ministry of Health, from 2020 to 2050, she said.

Several scenarios were explored, including some with patent extensions and data exclusivity, and a combination of those two TRIPS-plus measures, and the study showed a significant increase in public procurement budget if those measures were adopted.

Ukraine’s TRIPS-Plus Provisions

Oksana Kashyntseva of the National Institute of Intellectual Property of Ukraine said the trade agreement (Deep and Comprehensive Free Trade Agreement) between Ukraine and the EU has been costly.

In 2008, Ukraine signed TRIPS on the basis of TRIPS-plus provisions, she said, and until now, there has been no political will to implement TRIPS flexibilities into the national legislation. She described the Ukraine efforts on access to medicines, in particular the challenge of harmonising IP law, unfair competition law, and rights to access to medicines. Ukraine is working on an ongoing patent law reform.

Sergey Kondratyuk of the All-Ukrainian Network of People Living with HIV explained the court claim brought by Gilead against Europharma International, the Ukrainian Drug Regulation Authority and the Ministry of Health. The Gilead claim was based on data exclusivity protection.

In January, a settlement agreement was reached through which Ukraine had to cancel the marketing authorisation of granteziano (a generic version of original Gilead sofosbuvir), and protect Gilead’s rights. Gilead on its part had to set the price of sofosbuvir at US$250 for the government at least during the period of data exclusivity, and at US$349.90 for pharmacies, Kondratyuk said.

In December, Europharma won the lawsuit in first instance on restoring the generic sofosbuvir marketing authorisation, and Gilead served the Antitrust Committee of Ukraine with an application in investigation of concerted actions, he said.

Mohammed El Said, reader in International Trade and Intellectual Property Law at Lancashire Law School, at the University of Central Lancashire, United Kingdom, said there has been a lack of “real” innovation over decades in pharmaceutical products in terms of research and development. There has been however a rise in the number of granted patents, he said. Those patents do not have major value and contribution, he said.

Delinkage as Way Forward

In the audience, James Love of Knowledge Ecology International said the regulation of monopolies alone does not yield very strong results in terms of access to medicines. The issue of the costs involved in research and development should be addressed through delinkage of those costs from the end price of the medicines, he said. A growing number of people are focusing on the idea of separating the incentive from the price of drugs, Love said. High prices should not be a mechanism or an incentive for research and development, he said, adding that innovation should not be pitted against access.

By

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WHO position statement on the use of delamanid for MDR-TB http://www.eatg.org/news/who-position-statement-on-the-use-of-delamanid-for-mdr-tb/ Tue, 16 Jan 2018 22:59:42 +0000 http://www.eatg.org/?post_type=news&p=7202 15 January 2018 | Geneva: The World Health Organization (WHO) Global Tuberculosis Programme has released a Position Statement on the use of delamanid in treatment of multidrug-resistant tuberculosis (MDR-TB), following an expedited review of the phase III randomized controlled trial results released at the 48th UNION World Conference on Lung Health in Mexico by Otsuka Pharmaceutical.

“This trial is the first-ever MDR-TB treatment study of its kind to be completed and reported and its findings were thus much-awaited,” said Dr Tereza Kasaeva, Director of the Global TB Programme.

WHO acknowledges that the trial was conducted to high scientific standards, guided by an extensive and detailed study protocol, and with broad geographical distribution of study sites in seven countries (Estonia, Latvia, Lithuania, Republic of Moldova, Peru, the Philippines, and South Africa).

Trial participants received either delamanid or a placebo for six months, added to an optimised, longer background MDR-TB regimen designed according to WHO recommendations. Participants were randomised to receive either delamanid or placebo in a ‘blinded’ fashion, i.e neither they nor the treating physicians were aware of whether the medicine added to the MDR-TB regimen was active delamanid or an inactive placebo.

Overall, cure and mortality rates were similar in trial participants who received delamanid and in those who received the placebo on top of the optimised background MDR-TB regimen. The trial thus did not confirm the efficacy findings of earlier studies. However, no additional or new safety concerns were identified, providing reassurance of the safety of delamanid relative to many of the other second-line medicines used for MDR-TB treatment.

WHO is advising national TB programmes and other stakeholders to only add delamanid to a longer MDR-TB regimen when the regimen cannot be composed according to WHO recommendations, eg. when drug intolerability or drug resistance requires changes. When an effective and well-tolerated longer MDR-TB regimen can be otherwise composed, the addition of delamanid may not be warranted.

“MDR-TB trials are notoriously complex and difficult to do,” said Dr Karin Weyer, Coordinator of Laboratories, Diagnostics and Drug Resistance at the Global TB Programme. “We therefore commend the efforts of everyone involved, most importantly the MDR-TB patients who consented to participate. Research on the role of delamanid in MDR-TB treatment is important and should continue. In particular, the use of delamanid in MDR-TB regimens compromised by drug resistance or drug intolerability should be pursued”.

Delamanid should be retained in country guidelines, national essential medicine lists and procurement options, but MDR-TB treatment algorithms (and therefore procurement estimates) may need adjustment in view of the trial outcomes.

WHO is currently also conducting an expedited review of the STREAM Stage 1 interim results, another phase III randomized controlled trial, comparing a standardised shorter MDR-TB regimen to a longer MDR-TB regimen designed according to WHO recommendations.

Further to the expedited reviews of these two trials, WHO will conduct an extensive review of its MDR-TB policy guidelines this year. This will include a review of observational data for bedaquiline, delamanid and the shorter MDR-TB regimen conditionally approved by WHO, as well as a reassessment of the role of individual second-line medicines in MDR-TB regimens based on the latest patient and laboratory data.

 

WHO position statement on the use of delamanid for multidrug-resistant tuberculosis

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TB Europe Coalition releases two new publications http://www.eatg.org/news/tb-europe-coalition-releases-two-new-publications/ Tue, 16 Jan 2018 22:55:48 +0000 http://www.eatg.org/?post_type=news&p=7205 TB Europe Coalition released two new publications – an information brochure about the forthcoming United Nations High-Level Meeting on TB to be held in September this year, and a set of infographics.

The brochure explains what a United Nations High-Level Meeting is in general and what a United Nations High-Level Meeting on TB means, what the role of civil society is at global and regional level, and how civil society can get involved at national level before, during and after the meeting.

The infographics, produced in English and Russian, are an advocacy tool presenting the actual and projected economic impact of TB per country for the period 2000-2015 and till 2030, respectively in the World Health Organization European Region. The infographics are based on the KPMG report, The global economic impact of TB, released last year.

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HIV i-Base: HIV Treatment Bulletin, 5 January 2018 http://www.eatg.org/news/hiv-i-base-hiv-treatment-bulletin-5-january-2018/ Tue, 16 Jan 2018 22:50:45 +0000 http://www.eatg.org/?post_type=news&p=7208 HIV Treatment Bulletin (HTB) is a community publication produced by HIV i-Base. The publication starts 2018 with a new look: Shorter… faster… more often… More information here.

The online version of the first issue of HBT for 2018 is available at http://i-base.info/htb/date/2018/01.

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Factors associated with access to HIV testing and primary care among migrants living in Europe: cross-sectional survey http://www.eatg.org/news/factors-associated-with-access-to-hiv-testing-and-primary-care-among-migrants-living-in-europe-cross-sectional-survey/ Tue, 16 Jan 2018 22:45:09 +0000 http://www.eatg.org/?post_type=news&p=7209 ABSTRACT

Background

There is a heavy and disproportionate burden of human immunodeficiency virus (HIV) infection among migrant communities living in Europe. Despite this, the published evidence related to HIV testing, prevention, and treatment needs for migrants is sparse.

Objective

The aim of this study was to identify the factors associated with access to primary care and HIV testing among migrant groups living in Europe.

Methods

A Web-based survey (available in 14 languages) was open to all people aged 18 years and older, living outside their country of birth in the World Health Organization (WHO) European area. Community organizations in 9 countries promoted the survey to migrant groups, focusing on those at a higher risk of HIV (sub-Saharan Africans, Latin Americans, gay or bisexual men, and people who inject drugs). Multivariable analysis examined factors associated with access to primary care and previous history of an HIV test.

Results

In total, 559 women, 395 heterosexual men, and 674 gay or bisexual men were included in the analysis, and 68.1% (359/527) of women, 59.5% (220/371) of heterosexual men, and 89.6% (596/664) of gay or bisexual men had tested for HIV. Low perceived risk was the reason given for not testing by 62.3% (43/69) of gay or bisexual men and 83.3% (140/168) of women and heterosexual men who reported never having tested for HIV. Access to primary care was >60% in all groups. Access to primary care was strongly positively associated with living in Northern Europe compared with Southern Europe (women: adjusted odds ratio, aOR 34.56 [95% CI 11.58-101]; heterosexual men: aOR 6.93 [95% CI 2.49-19.35], and gay or bisexual men: aOR 2.53 [95% CI 1.23-5.19]), whereas those with temporary residency permits were less likely to have access to primary care (women: aOR 0.41 [95% CI 0.21-0.80] and heterosexual men: aOR 0.24 [95% CI 0.10-0.54] only). Women who had experience of forced sex (aOR 3.53 [95% CI 1.39-9.00]) or postmigration antenatal care (aOR 3.07 [95% CI 1.55-6.07]) were more likely to have tested for HIV as were heterosexual men who had access to primary care (aOR 3.13 [95% CI 1.58-6.13]) or reported “Good” health status (aOR 2.94 [95% CI 1.41-5.88]).

Conclusions

Access to primary care is limited by structural determinants such as immigration and health care policy, which varies across Europe. For those migrants who can access primary care and other health services, missed opportunities for HIV testing remain a barrier to earlier testing and diagnosis for migrants in Europe. Clinicians should be aware of these potential structural barriers to HIV testing as well as low perception of HIV risk in migrant groups.

To read the full publication, click here.


Bryan Teixeira, Secretary of the Board of Directors of the EATG, Koen Block, Executive Director of the EATG, and Alain Volny-Anne, Member of the EATG are among the authors of the publication.

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Hepatitis C treatment highly effective in harder-to-treat HIV coinfected patients, Spanish real-life study shows http://www.eatg.org/news/hepatitis-c-treatment-highly-effective-in-harder-to-treat-hiv-coinfected-patients-spanish-real-life-study-shows/ Tue, 16 Jan 2018 22:40:02 +0000 http://www.eatg.org/?post_type=news&p=7206

Hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) is highly effective and safe in harder-to-treat HIV co-infected patients, Spanish researchers report in AIDS. A sustained virological response (SVR), or cure, was observed in 93% of patients and only 0.4% stopped treatment because of adverse events. The large proportion of patients had advanced fibrosis or had taken a previous course of HCV therapy. Liver cirrhosis/liver stiffness were the only factors associated with treatment failure and use of ribavirin increased the risk of side-effects.

Nevertheless, 87.5% of people with cirrhosis achieved a sustained virologic response and no one with cirrhosis who completed a 24-week course of treatment and underwent follow-up testing failed to be cured of hepatitis C. The study findings are highly encouraging for coinfected people with advanced liver disease – in the past considered harder to treat – the study investigators conclude.

“The present work considered a heterogeneous, unselected cohort of coinfected patients who were treated for their HCV infection under normal clinical practice conditions, and contrasts well with highly-selective randomized clinical trials which do not always equate well to real-life settings,” write the investigators.

“The real-life results of studies performed in developed countries implementing all-oral DAA based regimens in cohorts principally including difficult-to-treat patients (HIV coinfected, cirrhotic, and/or with previous therapy failures), confirm these results.”

Approximately a third of HIV-positive patients in Spain are co-infected with HCV. Liver disease caused by HCV is a leading cause of serious illness and death in co-infected patients. In recent years, HCV therapy using all-oral DAA regimens has been developed. In clinical trials, these combinations have achieved SVR rates in excess of 90%. However, there is relatively little data about the efficacy and safety of DAA combinations in HIV/HCV-co-infected patients with characteristics usually associated with poorer treatment outcomes, especially more advanced liver disease or therapeutic failure using older regimens.

Investigators in eastern Spain therefore analysed outcomes in 515 co-infected patients who started an all-oral DAA regimen in 2015. Retrospective data were obtained on the proportion of patients attaining an SVR twelve weeks after completing a twelve or 24-week course of therapy, and also the proportion of patients experiencing adverse events. The investigators also conducted a series of analyses to see if specific patient or treatment factors were associated with the success of therapy or a greater risk of side-effects.

A total of 13 treatment centres in the region close to Valencia participated in the study. The patients had a median age of 50 years and 78% were male. Most (84%) had injecting drug use as their most likely mode of HCV infection. The most common HCV genotype was 1a (47%), with 20% carrying genotype 4 and 14% genotype 1b and 13% genotype 3. Just over half (54%) had cirrhosis, which was diagnosed using elastography (FibroScan, an assessment of liver stiffness) in 95% of patients. Just under half (46%) had taken a previous unsuccessful course of HCV therapy based on pegylated interferon or first-generation DAAs.

As regards HIV infection, 95% of individuals were taking antiretroviral therapy (ART) and 90% had a viral load below 50 copies/ml. Median CD4 cell count was 585 cells/mm3. To avoid potential drug interactions, a third of patients modified their ART before staring DAA therapy. The new combinations were mostly based on an integrase inhibitor.

The most widely used DAA regimen was ledipasvir/sofosbuvir (LDV/SOF; 57%). Just over third of patients (37%) were treated with a ribavirin-containing regimen and 7% took a 24-week course of therapy.

Overall, 93% of patients had sustained virological response twelve weeks after the completion of therapy.  There was little evidence that outcomes were influenced by baseline characteristics such as age and sex, HCV viral load or previous use of HCV therapy.

The only factors associated with reduced chances of attaining SVR were cirrhosis (p = 0.001) and liver stiffness above 21kPa (p = 0.001).

Only two patients (0.4%) stopped treatment because of adverse events, one because of decompensated cirrhosis, the other due to newly diagnosed high-grade lymphoma. Overall, 37% of patients reported any adverse events. These were mild in the majority of cases. Adverse events were reported by 54% of the ribavirin-treated patients, with 27% requiring dose reduction.

The investigators’ analyses failed to identify any significant association between specific DAA regimens and the risk of adverse events. However, ribavirin was associated with a nearly three-fold increased risk of side-effects.

“In real-life conditions, difficult-to-treated HIV/HCV-coinfected patients treated with all-oral DAA combinations reach high rates of SVR12, similar to those achieved by monoinfected patients in such conditions,” conclude the authors.

“Future drugs should be focused on reducing the risk of drug-drug interactions, along with an improvement in efficacy in patients with increased liver stiffness.”

By Michael Carter

Reference

Mínguez C et al. Interferon-free therapy for treating HCV in difficult-to-treat HIV-coinfected patients as implemented in routine medical practice. AIDS, online edition. DOI: 10.1097/QAD/0000000000001699 (2018).

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Hematopoietic stem cell transplantation safe in patients with HIV http://www.eatg.org/news/hematopoietic-stem-cell-transplantation-safe-in-patients-with-hiv/ Tue, 16 Jan 2018 22:30:07 +0000 http://www.eatg.org/?post_type=news&p=7207 An analysis of hematopoietic stem cell transplant recipients in the United States over a 14-year period showed that patients with HIV do not have an increased risk for serious in-hospital complications despite having a potentially higher risk for certain opportunistic infections.

Research has demonstrated that patients with HIV are living longer because of the availability of highly active ART. This has led to an increase in the incidence of HIV-associated malignancies as well as hematopoietic stem cell transplantation (HSCT) to treat these malignancies, according to Kathan Mehta, MBBS, MPH, resident physician in the division of hematology-oncology at the University of Pittsburgh Medical Center, and colleagues.

Although previous studies have shown that HSCT outcomes are similar between HIV-positive and HIV-negative patients, Mehta and colleagues noted that these studies are limited by their small sample sizes and lack of recent data. Therefore, the researchers assessed the outcomes of 39,517 patients who underwent allogeneic or autologous HSCT from 1998 to 2012 to better understand the risks associated with HSCT among patients with HIV. The primary outcome was the rate of in-hospital mortality among HIV-positive and HIV-negative patients.

According to the data, the number of patients with HIV undergoing HSCT in the U.S. has continuously increased from 81 patients between 1998 and 2002 to 278 patients between 2008 and 2012.

For allogeneic HSCT, patients with HIV were more likely to have nontuberculous mycobacteria (5.4% vs. 0.2%; P < .0001) and cytomegalovirus infection (22.2% vs. 6.3%; P = .04) than patients without HIV. However, there was no significant difference in the incidence of intubation (6.1% vs. 8.2%), sepsis (28.8% vs. 13.1%), bacteremia (40.2% vs. 23.3%), graft-versus-host disease (22.9% vs. 17.9%), total parenteral nutrition (TPN) use (11.8% vs. 23.4%) and venous thromboembolism (VTE; 11% vs. 4.5%).

Similarly, for autologous HSCT, there was no significant difference between groups for intubation (3.1% vs. 2.5%), sepsis (6.3% vs. 8.1%), bacteremia (10.7% vs. 16%), TPN use (9% vs. 13.1%) and VTE (2% vs. 3.7%).

In a multivariate analysis, there was no significant difference in inpatient mortality between the groups for both allogeneic (OR = 1.27; 95% CI, 0.44-3.66) and autologous (OR = 0.95; 95% CI, 0.26-3.49) HSCT.

“In summary, frequency of HSCT is increasing in HIV-positive patients with underlying indication for HSCT,” the researchers concluded. “Allogeneic and autologous HSCT can be safely performed in HIV-positive patients.”

Mehta K, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy010.

By Stephanie Viguers

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Investigation questions transparency for failed TB vaccine http://www.eatg.org/news/investigation-questions-transparency-for-failed-tb-vaccine/ Tue, 16 Jan 2018 18:11:03 +0000 http://www.eatg.org/?post_type=news&p=7203

The BMJ inquiry finds that researchers presented only select results from animal experiments when applying for funding and approval for human trials.

Oxford University scientists developing the MVA85A vaccine, intended as a booster to the established Bacille Calmette-Guerin (BCG) tuberculosis (TB) vaccine, misrepresented preclinical results to obtain funding and approval for a 2009 clinical trial in South Africa that failed to show any benefit, according to an investigation published in The BMJ yesterday (January 10).

In applications provided for funding and ethical and regulatory approval of the trial, as well as in the information given to parents enrolling their children as participants, the researchers included claims that the MVA85A booster had proven safe and more protective than BCG alone in multiple animal models. But according to the investigation, the team was “privately playing down or dismissing unsupportive experiments as ‘failed’ or irrelevant,” writes Deborah Cohen, associate editor at The BMJ. Indeed, a 2015 review by researchers at Stellenbosch University in South Africa found that animal study results for MVA85A did not support its use as a BCG booster.

Ewan McKendrick, registrar of Oxford University, tells The Independent that three separate investigations by Oxford University cleared the researchers of “any wrong-doing,” and adds that the team had “observed the highest scientific and ethical standards.” But if the researchers really did lack transparency in reporting the preclinical results for the MVA85A vaccine, it isn’t an isolated incident, Jonathan Kimmelman of the Biomedical Ethics Unit at McGill University in Canada notes in a press release. “Unfortunately, there are other cases where new treatments were put into human testing on animal evidence that was foreseeably flawed, incomplete, or even negative.”

Speaking with MedPage Today, Kimmelman says that not only do regulators sometimes fail to recognize the fallibility of promising animal findings, but that some may even actively overlook equivocal or negative results. “Research programs are like supertankers,” he says. “Once they are up and running they have their own momentum, and it is really, really difficult to stop them.”

Another part of the problem may be the lack of oversight of preclinical research, for which there is no central registry like there is for clinical trials, Malcolm Macleod of the University of Edinburgh writes in an editorial in The BMJ accompanying the investigation. “We need to develop better and more systematic ways to establish when a drug is ready for clinical trials in humans—and importantly, when it is not.”

By Jef Akst

 

Read also:

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Ukraine to finance expanded opioid substitution therapy programme http://www.eatg.org/news/ukraine-to-finance-expanded-opioid-substitution-therapy-programme/ Mon, 15 Jan 2018 22:59:22 +0000 http://www.eatg.org/?post_type=news&p=7190

The Government of Ukraine has committed to fund and expand access to opioid substitution therapy (OST) for over 10 000 patients at 178 health-care facilities in 2018. This represents a 100 fold increase in the number of OST patients in Ukraine since 2005.

OST is a globally recognized intervention to reduce injecting behaviours that put people who inject drugs at risk of contracting HIV and other blood-borne diseases, such as viral hepatitis. OST reduces opioid use, increases retention in HIV treatment and improves the well-being and social functioning of people who inject drugs, aiming at prevention of transmission of HIV. In 2018, the Ukrainian government takes over financial support of the OST programme from international donors, making it the largest of its kind in eastern Europe and central Asia.

“This marks an important milestone for public health in Ukraine”, comments Martin Donoghoe, Senior Adviser for TB, HIV and Hepatitis in the WHO Country Office in Ukraine.  “WHO and partners have been working together with the government for many years to finally see OST accepted and financially supported. This shows that Ukraine is fully committed to respond to HIV.”

The continued success of the OST programme has been made possible by more than 12 years of work by international agencies including WHO and partners, international and domestic nongovernmental organizations, the Ministry of Health of Ukraine and health-care facilities in raising awareness, training staff, engaging patients, procuring and distributing medications to the regions, and protecting the rights of patients.

OST financing is not the sole achievement. Over 80 000 people have been put on antiretroviral therapy (ART) and a new protocol is in the pipeline moving Ukraine towards full optimization of HIV treatment. “With the recent approval of a Global Fund grant on treatment optimization for key populations this could be the turning point for the HIV response in Ukraine”, Donoghoe concludes.

“OST has saved my life”

The government’s announcement took place on 20 December 2017, at Kyiv City Narcological Hospital, which has the highest number of OST patients in Ukraine. Anton Basenko, one of the patients, tells his story.

“OST has saved my life. It has returned me to my family, I have married my girlfriend and we are planning to have children. Finally, OST has made me what I am, an employee of an international organization and a representative of the community of people who inject drugs and OST patients at the National Council to Fight Tuberculosis and HIV/AIDS”, Anton says.

“Every one of the over 10 000 patients on OST can tell their positive story”, continues Anton. “Yet we should not forget that all these lives were saved through the financial support of international donors. However, this funding cannot be provided forever, and without state support, all these people are doomed.”

He concludes: “Today, we are really happy that the government has decided to provide funds to procure OST medications for drug-dependent people. It is important that this procurement is stable and is accompanied by the psychosocial support we need”.

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War in Ukraine has escalated HIV spread in the country http://www.eatg.org/news/war-in-ukraine-has-escalated-hiv-spread-in-the-country/ Mon, 15 Jan 2018 22:57:55 +0000 http://www.eatg.org/?post_type=news&p=7199 Conflict in Ukraine has increased the risk of HIV outbreaks throughout the country as displaced HIV-infected people move from war-affected regions to areas with higher risk of transmission, according to analysis by scientists.

Ukraine, which has the highest HIV prevalence in Europe, has been at war since 2014 following political unrest in the country.

An international team of scientists led by Oxford University and Public Health England (PHE) analysed genetic sequences to reconstruct viral migration patterns and found that the war-related movement of 1.7 million people was associated with the dissemination of HIV in Ukraine – and that areas with a high prevalence of risky sexual behaviour were the main recipients of the virus.

The research is published in the journal PNAS. The study was part-funded by the Medical Research Council (MRC).

Lead author Tetyana Vasylyeva, a PhD candidate in Oxford University’s Department of Zoology, said: ‘In a country of 45 million people, an estimated 220,000 are infected with HIV – the highest prevalence in Europe. The epidemic started in the 1990s with an explosive rise in the number of new infections in people who inject drugs, but today 70-80% of new infections are reported to be in heterosexual people who don’t inject drugs. It is a silent epidemic, because about 50% of HIV-infected people are unaware of their infection status and around 40% of newly diagnosed people are in the later stages of the disease.

‘In this study we found that virus migration has increased rapidly and follows a westward pattern. Donetsk and Lugansk, two large cities in the east of Ukraine that have not been controlled by the Ukrainian government since 2014, are the main exporters of the virus. We find evidence for a spatial “redistribution” of pre-existing infections, rather than new transmissions. Indeed, the observed movement of the virus into given regions was correlated with the number of HIV-infected internally displaced people moving to that region.’

The study’s findings, based on data collected between 2012 and 2015, are in line with previous work on the spread of HIV throughout the western world, which was shown to have mirrored geopolitical events.

Senior author Dr Gkikas Magiorkinis, formerly of Oxford University/PHE and now of the National and Kapodistrian University of Athens, said: ‘This study provides evidence that the movement of people in Ukraine during the war was followed by increased risk of HIV transmission. Our analysis suggests that harm reduction services should be scaled up in order to prevent further transmission of HIV in the country, and that international support should be provided to prevent a potential new public health tragedy.

‘We also observed that in 2015 the prevalence of virus resistance against drugs that can be used for pre-exposure prophylaxis (PreP) was 34%, which seems much higher than other European countries. PreP is a drug treatment that can prevent HIV infection in people who are at substantial risk and has recently emerged as an important public health strategy to control the spread of HIV. Our findings suggests that in Ukraine this method could be undermined in the near future. Further work is needed to confirm this worrying preliminary observation.’

Dr Jonathan Pearce, Head of Infections and Immunity at the MRC, said: ‘Studies that shed light on how a disease is spread are important to enable development of effective prevention strategies. In this example, we see how the displacement of people as a result of man-made disaster, war, is contributing to the increased spread of HIV in Ukraine. This understanding will help officials shape public health practices to better manage and prevent HIV infection.’

Tetyana Vasylyeva added: ‘The war and internal migration in Ukraine has created a worrying epidemiological situation: new HIV strains might be moving at a higher rate to regions where the conditions for onward transmission are most appropriate. The work being done to enable the smooth running of treatment and prevention services in occupied regions is therefore of critical importance. Recently relocated people should be linked to care and harm reduction services, and there needs to be additional support for NGOs and medical facilities to help monitor and prevent local outbreaks in the central and southern regions of Ukraine.’

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Johns Hopkins is the first center in the U.S. to be approved for living donor HIV-positive to HIV-positive kidney transplants http://www.eatg.org/news/johns-hopkins-is-the-first-center-in-the-u-s-to-be-approved-for-living-donor-hiv-positive-to-hiv-positive-kidney-transplants/ Mon, 15 Jan 2018 22:55:09 +0000 http://www.eatg.org/?post_type=news&p=7194 Living kidney donors are currently being evaluated for this medical milestone

Approximately 122,000 people are on the transplant waiting list in the U.S. at any one time. Allowing HIV-positive living organ donation could help change that.

Johns Hopkins hopes to become the first hospital in the United States to perform HIV-positive to HIV-positive organ transplants from living donors.

A comprehensive medical and psychological screening and evaluation to identify potential risks is done for any individual who is interested in donating an organ, and potential kidney donors are currently being evaluated for this medical milestone. A previous study led by Dorry Segev, associate professor of surgery at the Johns Hopkins University School of Medicine, found that long-term mortality was similar or lower for live kidney donors than their counterparts in the general public. Once a donor is identified, then a suitable recipient, who is currently on the kidney waiting list, will be selected and the procedures will be scheduled.

“This is an unbelievably exciting time for our hospital and our team, but most importantly, it’s a hopeful time for patients living with HIV and end-stage organ disease,” Segev says. “Organ transplantation is actually even more important for patients with HIV, since they die on the waiting list even faster than their HIV-negative counterparts. For these individuals, it can mean a new chance at life and a larger pool of organs.”

Approximately 122,000 people are on the transplant waiting list in the United States at any one time; nearly 96,000 of these are on the kidney waitlist. Thousands die each year, many of whom may have lived had they gotten the organ they needed. Meanwhile, Segev estimates that each year, about 500 to 600 HIV-positive, would-be organ donors had organs that could have saved more than 1,000 people—if only the medical community was allowed to use the organs for transplant.

In 2016, Segev led the Johns Hopkins team that completed the first ever HIV-to-HIV liver and kidney transplants from deceased donors in the U.S.

The first approved HIV-positive to HIV-positive living donor kidney transplant will take place as soon as a suitable donor is approved and a recipient is successfully identified and prepared.

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HIV does not increase aging-related brain changes in patients on ART http://www.eatg.org/news/hiv-does-not-increase-aging-related-brain-changes-in-patients-on-art/ Mon, 15 Jan 2018 22:54:44 +0000 http://www.eatg.org/?post_type=news&p=7197 Researchers said they found no evidence that HIV accelerates aging-related brain changes over a 2-year period in middle-aged patients on successful ART.

“This provides reassurance that, with virological suppression, [people living with HIV (PLWH)] in middle age are not at increased risk of progressive cognitive decline and abnormal deterioration to brain health over 2 years,” James H. Cole, PhD, honorary research fellow in the division of brain sciences at Imperial College London and department of neuroimaging, Institute of Psychiatry, Psychology and Neuroscience at King’s College London, and colleagues wrote in Clinical Infectious Diseases.

Although combination ART (cART) has substantially reduced AIDS-related morbidity and mortality, PLWH continue to experience higher rates of neurological, cardiovascular, renal, hepatic and pulmonary disease, as well as cancer, osteoporosis and physical frailty. Because these conditions typically increase with age, there is concern that age-related deterioration may accelerate in PLWH, despite cART, according to the researchers.

Few longitudinal neuroimaging studies have investigated accelerated brain changes and cognitive decline in PLWH. Some have demonstrated accelerated brain pathology; however, Cole and colleagues noted that these studies have important limitations. Therefore, the researchers conducted a multicenter, longitudinal study involving 134 virologically suppressed PLWH (median age, 56 years) and 79 demographically matched HIV-negative controls (median age, 57.2 years) to clarify whether PLWH on cART have increased changes in age-related neuroimaging measures.

All study participants completed neuropsychological assessments and underwent multimodality neuroimaging during a baseline and 2-year follow-up visit. The researchers hypothesized that MRI measures would be abnormal among PLWH at baseline; that PLWH would have greater rates of change in MRI metrics vs. HIV-negative controls over 2 years; and changes in MRI metrics would be associated with a decline in cognitive function, despite cART.

At baseline, the researchers reported that PLWH had inferior global cognitive performance (P < .01), lower gray matter volume (P = .04), higher white matter hyperintensity load (P = .02), abnormal white matter microstructure (P < .005) and greater “brain-predicted age difference” (P = .01). Over the 2-year follow-up period, neuroimaging measures showed that both PLWH and controls experienced similar reductions in brain volumes, altered white matter structure, increased white matter hyperintensity load and reduced cerebral perfusion. The researchers also observed similar changes in neuropsychological tests between the groups. Cognitive performance, they reported, remained stable over time.

“Our results indicate that in PLWH on suppressive cART, any progressive changes to the brain that occur are no greater than those seen in appropriately matched HIV-negative controls,” the researchers concluded. “To better understand trajectories of cognitive aging in PLWH, future studies would benefit from larger numbers, more frequent assessments and run-in periods to mitigate practice effects.”

Cole JH, et al. Clin Infect Dis. 2018;doi:10.1093/cid/cix1124.

By Stephanie Viguers

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Faster action on adherence is needed after viral load becomes detectable, researchers warn global treatment programmes http://www.eatg.org/news/faster-action-on-adherence-is-needed-after-viral-load-becomes-detectable-researchers-warn-global-treatment-programmes/ Mon, 15 Jan 2018 22:53:32 +0000 http://www.eatg.org/?post_type=news&p=7187

Low-level HIV viral load, above the limit of detection, is an important warning signal for future treatment failure and World Health Organization guidelines on spotting treatment failure need to be revised to encourage greater vigilance and swifter action by healthcare providers in lower- and middle-income settings, investigators report in The Lancet Infectious Diseases.

The study, carried out by Annemarie Wensing and colleagues at the University of Utrecht in the Netherlands and University of Witwatersrand in South Africa, looked at the relationship between having a detectable viral load below 1000 copies/ml after at least six months on antiretroviral treatment and the subsequent risk of treatment failure – a virological rebound above 1000 copies/ml that should lead to a switch in treatment.

In its 2016 antiretroviral treatment guidelines for lower- and middle-income settings, the World Health Organization (WHO) did not recommend any action should be taken in cases where a person has a detectable viral load below 1000 copies/ml. WHO recommends that people should switch to second-line antiretroviral treatment after two consecutive viral load measurements above 1000 copies/ml.

But in European and United States treatment guidelines, intervention is recommended if viral load rises above 50 copies/ml.

Low-level viraemia – above the limit of detection of a viral load test but below 1000 copies/ml – may increase the risk of subsequent treatment failure but studies in Europe and North America have come to contradictory conclusions and do not provide enough information to judge whether any level of detectable viral load predicts failure, or only viral loads above 500 copies/ml. Low-level viral load may emerge as a result of problems in adherence to treatment, or short periods of disengagement from treatment and care.

To investigate how many people experience episodes of low-level viraemia, and the extent to which low-level viraemia predicts a rise in viral load above 1000 copies/ml and subsequent treatment failure, investigators looked at people receiving treatment at 57 clinics within South Africa’s public sector HIV treatment programme.

The observational study looked at all people receiving treatment between 2007 and 2016 who had virological follow-up data after starting treatment, a total of 70,930 people. Virological monitoring took place six months after starting treatment, 12 months after starting treatment and every 12 months thereafter.

Study participants were followed for a median of 124 weeks if on first-line treatment and 101 weeks if on second-line treatment; 41% of those on first-line treatment and 31% of those on second-line treatment were followed for more than three years.

The incidence of low-level viraemia was high: 23% of people had at least one viral load measurement above 50 copies/ml and below 1000 copies/ml. The remainder had either two or more intermittent measurements (8%) or two or more consecutive measurements (13%). In 59% of first-line antiretroviral therapy (ART) patients and 55% of second-line ART patients, the viral load measurement was in the range of 50-199 copies/ml.

Virological failure occurred in 22% of first-line ART patients and was more likely to occur during the first year of treatment. As the analysis excluded people who had virological failure at the time of their first viral load test, this finding suggests a need for adherence support in the first year of treatment that extends beyond the early months of treatment.

In an analysis that included only those people with more than a year of viral load follow-up and which excluded those with only one viral load result, any episode of low-level detectable viraemia was associated with a significantly increased risk of treatment failure. The risk ranged from a hazard ratio of 1.9 for a viral load of 51-199 copies/ml compared to having undetectable viral load, to a hazard ratio of 4.7 for a viral load in the range 400-999 copies/ml (< p = 0.0001) for people on first-line treatment. In people taking second-line treatment a similar pattern held true: a hazard ratio of 2.1 for a viral load of 51-199 copies/ml and a hazard ratio of 6.8 for a viral load in the range 400-999 copies/ml (P < 0.0001).

Treatment failure was more likely after two consecutive measurements of low-level viraemia than either a single measurement of low-level viraemia or intermittent low-level viraemia.

The study also found that people who had treatment failure preceded by low-level viraemia were less likely to achieve viral resuppression on their first-line regimen (adjusted odds ratio 0.92) and more likely to need to switch to second-line treatment (aOR 1.02) when compared to people who experienced treatment failure without any previous evidence of low-level viraemia.

A total of 3854 people met the criteria for a switch to second-line treatment; 41% eventually switched treatment. They spent a median of 59 weeks with viral load above 1000 copies/ml before being switched to second-line treatment (current guidelines recommend that the switch should take place no more than 12 weeks after the first detection of virological failure).

“Our results show that any detectable viral load between 51 and 999 copies per ml leads to poorer treatment outcomes than successful virological suppression of less than 50 copies per ml,” write the investigators.

“We recommend that WHO guidelines explicitly incorporate low-level viraemia as an early warning signal that deserves clinical action, including intensification of adherence counselling and repeat viral load testing.”

The authors dismiss the idea that adoption of drugs with a higher genetic barrier to development of resistance will minimise the risk of treatment failure, pointing out that patients on second-line regimens containing a boosted protease inhibitor were just as likely to experience treatment failure as people on first-line treatment containing a non-nucleoside reverse transcriptase inhibitor after low-level viraemia.

A potential obstacle to improving detection of treatment failure lies in the adoption of point-of-care viral load assays and dried-blood spot sampling that may not be able to detect viral load below 1000 copies/ml, the authors note.

In an accompanying Comment article, Antonella Castagna and Laura Galli of San Raffaele University, Milan, emphasise the importance of improving adherence support, especially the elimination of structural barriers to adherence such as restrictions on medication pick-up from clinics, monthly dispensing of medication and greater distances to travel to collect medication.

By Keith Alcorn

Reference

Castagna A & Galli L. Stepping up HIV-1 low-level viraemia surveillance in South Africa. The Lancet Infectious Diseases, advance online publication, 17 November 2017.

Hermans L et al. Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes. The Lancet Infectious Diseases, advance online publication, 17 November 2017.

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Mother-to-child HIV transmission higher when mother has other STIs http://www.eatg.org/news/mother-to-child-hiv-transmission-higher-when-mother-has-other-stis/ Mon, 15 Jan 2018 22:52:43 +0000 http://www.eatg.org/?post_type=news&p=7195 A new study confirms that HIV-infected pregnant women have a higher risk of transmitting the HIV to their infants if the mothers also have another sexually transmitted infection.

The research found the highest risk, by a significant margin, came when the mother was co-infected with cytomegalovirus (CMV).

Kristina Adachi, MD, MA, a clinical instructor in the Department of Pediatrics, Division of Infectious Diseases, at the University of California, Los Angeles, said the findings add to existing evidence that STIs can have adverse effects on pregnant women with HIV, and on their babies.

“In general, I think the study helped provide additional support for the idea that having STIs in pregnancy may increase the risk of HIV MTCT (mother-to-child transmission),” Adachi told MD Magazine. “There have not been many published studies that specifically looked at this relationship.”

Adachi and her co-authors tested 899 mother-infant pairs, checking the mothers for common STIs, and the babies for HIV. Nearly one third (30%) of the mothers tested positive for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP) and/or CMV at delivery. Among the infants, 9.1% tested positive for HIV.

HIV transmission rates varied depending on the specific infection found in the mother. Most prominent was the finding that when the mother tested positive for CMV, mother-to-child transmission occurred in 26.3% of cases. The next closest transmission rate was among women with Chlamydia trachomatis, of whom 12.5% passed HIV along to their infants.

Overall, 42% of HIV-infected infants were born to mothers with 1 of the 4 STIs, and women with an STI were nearly twice as likely to pass on HIV as women without an STI. The rates were highest among women with 2 of the 4 STIs.

Adachi is part of the HIV Prevention Trials Network’s HPTN-040 research group. She said previous research by the group has found associations between individual STIs and mother-to-child transmission of HIV, including chlamydia, syphilis and CMV viruria.

As for why the CMV association appears to be so strong, Adachi said the relationship between CMV and HIV is more complex than that of other STIs.

“The presence of CMV has the potential to impact the severity of HIV infection and viral replication and vice versa,” she said. “Specifically, it is thought that CMV may also lead to placental inflammation, which may facilitate HIV MTCT. In addition, CMV may also lead to upregulation of co-receptors that increase the likelihood of HIV infection.”

As far as the clinical implications, Adachi noted that Chlamydia, gonorrhea, and syphilis can cause other, even fatal, problems besides mother-to-child transmission, so it’s important that those STIs be treated in pregnant women generally, not just pregnant women with HIV.

“Unfortunately, at this time there are not good treatment options for primary infection with CMV in pregnancy,” she said.

Asked if treatment of STIs might result in a lower risk of mother-to-child transmission, Adachi said that specific question has not been studied extensively, but 1 study that did probe the issue found STI treatment improved pregnancy outcomes but did not affect mother-to-child transmission rates.

Adachi’s study is titled “Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission.” It was published last week in PLOS One.

By Jared Kaltwasser

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One-time routine HIV screening at age 25 optimal with no risk factors http://www.eatg.org/news/one-time-routine-hiv-screening-at-age-25-optimal-with-no-risk-factors/ Mon, 15 Jan 2018 22:45:19 +0000 http://www.eatg.org/?post_type=news&p=7193 For young adults without known risk factors, a one-time routine HIV screen at 25 years would optimize clinical outcomes and be cost-effective, according to a study published in the Journal of Adolescent Health.

Anne M. Neilan, MD, MPH, from Massachusetts General Hospital in Boston, and colleagues simulated HIV-uninfected 12-year-olds without identified risk factors who faced age-specific HIV infection risks. The authors modeled a one-time HIV screen ($36) at age 15, 18, 21, 25, or 30 years, each in addition to current US screening practices (30% screened by age 24).

The researchers found that all one-time screens detected a small proportion of lifetime infections (0.1% to 10.3%).

A screen at 25 years led to the most favorable care continuum outcomes at age 25 compared to current screening practices, with a higher proportion diagnosed (77% vs 51%), linked to care (71% vs 51%), retained in care (68% vs 44%), and virologically suppressed (49% vs 32%). A screen at age 25 years not only provided the greatest clinical benefit but also was cost-effective ($96,000/year-of-life saved [YLS]) by US standards of <$100,000/YLS compared with the next most effective screen.

“Focusing screening on adolescents and young adults ages 18 or younger is a less efficient use of a one-time screen among AYA than screening at a later age,” the authors write.

Reference

Neilan Am, Dunville R, Ocfemia MCB, et al. The optimal age for screening adolescents and young adults without identified risk factors for HIV. J Adolesc Health. 2018 Jan;62(1):22-28.

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Positive LAM results predict mortality in children with HIV http://www.eatg.org/news/positive-lam-results-predict-mortality-in-children-with-hiv/ Mon, 15 Jan 2018 21:49:52 +0000 http://www.eatg.org/?post_type=news&p=7192 Children with HIV in Kenya whose urine samples tested positive for lipoarabinomannan, or LAM — a biomarker of tuberculosis — had a nearly fivefold increased risk for mortality compared with children with negative LAM results, according to recent data.

The association between positive LAM results and mortality was particularly high in children with unconfirmed TB, which suggests that the antigen may identify children at risk for death whose TB infection may have been missed by respiratory sampling, Sylvia M. LaCourse, MD, MPH, acting instructor in the department of medicine, division of allergy and infectious diseases at the University of Washington, Seattle, and colleagues reported in Clinical Infectious Diseases.

LAM is a component of the Mycobacterium tuberculosis cell wall that is detectable in the urine of patients with TB, according to the researchers. LAM testing is performed with a low-cost, point-of-care assay that uses a dipstick to detect the antigen. WHO recommends LAM testing in patients with HIV who have a low CD4 count or are critically ill. Previous data has shown that adults coinfected with HIV and TB who test positive for LAM have twice the risk for morality compared with adults who test negative for LAM. However, less is known about LAM’s prognostic performance for mortality in children, the researchers noted.

“The underlying pathway between LAM and TB mortality is not completely clear,” they wrote. “LAM may be a marker of disseminated TB or higher mycobacterial burden, both associated with worse prognosis. Additionally, LAM may function as a virulence factor, inhibiting macrophage function and proinflammatory cytokines, and enhancing anti-inflammatory cytokines.”

For their study, LaCourse and colleagues examined data from 137 hospitalized children (median age, 26 months) with HIV initiating ART — a population in which TB is often overlooked, according to the researchers. All participants provided urine samples for LAM testing and sputa or gastric aspirates, which were cultured for TB.

Among the cohort, 6.6% of children had confirmed TB and 43.1% had unconfirmed TB. Eleven percent of children had positive LAM results, including 33.3% with confirmed TB and 20% with unconfirmed TB. Over a 6-month follow-up period, 15.3% of children had died.

The 6-month risk for mortality was higher in children with positive LAM results vs. those with negative LAM results (adjusted HR = 4.92; 95% CI, 1.79-13.49). Among children with unconfirmed TB, a positive LAM result was associated with a 10-fold increased risk for mortality (HR = 10.4; 95% CI, 0.94-115.18).

“These children may benefit from treatment even in the absence of microbiologically confirmed TB, and urine LAM could reduce time to treatment in children at highest risk for death,” the researchers noted.

Positive LAM results also predicted mortality among children with HIV-related severe immunosuppression (HR = 4.69; 95% CI, 1.73-12.70) and malnutrition (HR = 5.35; 95% CI, 1.03-27.70).

“These data provide evidence to support WHO’s recommendation that urine LAM is helpful for TB diagnosis in severely ill HIV-infected children, including those at greatest mortality risk,” the researchers concluded. “Future studies are needed to confirm whether incorporation of urine LAM can prevent mortality in HIV-infected children.”

LaCourse SM, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy011.

By Stephanie Viguers

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Attitudes towards men who ‘bareback’ are a barrier to wider use of PrEP http://www.eatg.org/news/attitudes-towards-men-who-bareback-are-a-barrier-to-wider-use-of-prep/ Mon, 15 Jan 2018 21:31:18 +0000 http://www.eatg.org/?post_type=news&p=7188

Two new qualitative studies from Toronto shed light on how stigma affects the uptake of pre-exposure prophylaxis (PrEP) and the experience of taking it. In the first, young gay men acknowledged that they did not always use condoms but did not see themselves as the kind of ‘barebacker’ for whom they thought PrEP was intended.

“PrEP embodies the notion of bareback sex, which traditionally has been associated with negative elements, and it is quite clear that the young gay men in this research do not want to be associated as a barebacking subject,” writes Julien Brisson in Anthropology & Medicine. “This is one reason why they did not want to use PrEP.”

In the second study, early adopters described concealing their PrEP use because of what it might suggest to others about their sexual behaviour. Nonetheless most had an overwhelmingly positive experience of taking PrEP.

“Paradoxically, some men said that PrEP use both led them to experience stigmatizing reactions within their social and sexual networks, while also helping to remove stigma, shame, and fear related to HIV, sexuality, and sex with gay men living with HIV,” comments Daniel Grace in AIDS Patient Care and STDs.

Young gay men’s feelings about barebacking and PrEP

Julien Brisson of the University of Montreal conducted ethnographic fieldwork with young gay men in a gay neighbourhood of Toronto. As well as in-depth interviews with ten men, he reports on informal interactions at gyms, social events, an LGBT film festival and meetings about HIV prevention. Most of his informants were in their twenties and well-educated, although his interview sample was ethnically diverse.

The research was conducted in 2014, before PrEP was approved by Canadian regulators in February 2016. This was also before PrEP was added to Ontario’s provincial drug programme in September 2017, a move that has facilitated access to PrEP in Toronto, especially for people on low incomes.

The men taking part in the research were generally well-informed about HIV prevention. Having had their first sexual relations in the 2000s, they were highly aware of HIV prevention messages about condoms. They were also knowledgeable about the biomedical science relating to HIV prevention, often using pragmatic techniques such as ‘serosorting’ and ‘strategic positioning’ to diminish the risk of HIV transmission when they did not use condoms.

Of note, on the first occasions that the researcher met his respondents, they all reported that they did not have bareback sex. They tended to express the idea that it was a bad and reckless practice. In line with the way in which medical and psychological researchers have represented men who bareback, the young gay men often described barebackers as people who had problems with depression, self-esteem or drug use.

For example, Brisson describes meeting a 25-year old at a party and explaining that his research was on bareback sex. The young man said with a tone of pride that he was a responsible person who always used condoms, while other men attending the party nodded in approval or said that they did the same.

Nonetheless, a few weeks later, the same man took part in an in-depth interview. This revealed both the man’s accurate knowledge of biomedical information about HIV transmission and his engagement in condomless sex. He said:

“I do get tested regularly, and I’m aware of the transmission risks of HIV. I’m not aware of the exact numbers, but I know, even if the person is HIV-positive and on ART and I’m the top [insertive partner], which I generally am, the risk is very low for me.”

Another man expressed pride in his knowledge of HIV prevention and his apparently consistent use of condoms when he first met the researcher. During the course of the fieldwork, the researcher was often present when the man shared detailed and entertaining stories about his sexual adventures with friends. Eventually, the man began to talk with the researcher about sexual practices that did not always involve condoms.

However, like the first man described, he was not interested in using PrEP. As he felt that he was ‘responsible’ when he did not use condoms, he did not think that PrEP would be right for him, as this interview transcript shows:

– No, I think that I am a little bit smarter about the disease, and I don’t think that I’m subjected to the disease as much as I am aware of it, so I don’t think it’s necessary for me to take a pill a day.

– No? Even though you like bareback sex?

– No, I love it! But I think that I am smart enough to know who to have it with.

– OK, so you would not take [PrEP] even though it prevents HIV?

– No, even though it sounds amazing, I don’t think I’m a high-risk individual, I don’t consider myself a high-risk individual, even though I’m gay and I enjoy partaking in bareback sex. I would not consider myself a high-risk individual, not today, not tomorrow.

– So is it because it is meant for high-risk groups that you would not take [PrEP]?

– I don’t think that I am. I don’t think that’s something for me – maybe for somebody else, but not for me.

None of the young gay male informants were interested in using PrEP at the time of the research. They supported other people using PrEP and rejected the stigmatisation of PrEP users as ‘Truvada whores’. But they tended to see themselves as different from potential PrEP users.

“If you wanna take the Truvada in order to have bareback sex, fine… If you believe that’s the right thing to do, I’m not the one to tell you you are wrong or to criticise… If you are doing it, I just hope you really understand the risks and what you are doing to yourself, and if it’s safe, good, amazing, good for you. Good too that you can have something in order to enjoy sex more if you need to have bareback sex.”

Julien Brisson argues that the contradictory meanings associated with PrEP made it harder for his respondents to imagine themselves using it. “PrEP embodies the idea of ‘HIV prevention’, which is attached to virtuous qualities, and PrEP simultaneously represents the idea of bareback sex, which has traditionally been saturated with problematic elements,” he says.

PrEP users’ experiences of stigma

The second study was also conducted in Toronto, but a year or two later, and with a different group of participants – gay men of a range of ages who had taken part in a PrEP demonstration project in the city. As such, they can be considered ‘early adopters’ of PrEP, who are likely to be enthusiastic about its potential.

Daniel Grace of the University of Toronto and colleagues conducted focus groups and individual interviews with a total of 16 gay men. Most were white and almost all were university educated. Four respondents were in their twenties, seven in their thirties, two in their forties, and three in their fifties.

The men reported that they had to manage other people’s assumptions about why they were using PrEP. Generally, people in the men’s social and sexual networks equated PrEP use with having condomless sex. Some participants described how PrEP-related stigma, or stigma related to having multiple sexual partners, had led them not to tell family or friends about taking PrEP, creating a kind of ‘PrEP closet’.

This man said that he did not discuss using PrEP as it would invite other people to make judgements about the non-monogamous relationship he has with his husband.

“I don’t disclose that I am on PrEP to most family and most friends. That’s maybe because I am married and I have kids, so for his [husband’s] sake, I am not really, we are not open—fully open that we’re open if you know what I mean. So I mean I should be able to be, but I don’t think we’re there yet. So I wouldn’t say that I feel ashamed for it but I definitely have to hide it.”

Stigmatising responses could also come from sexual partners.

“There were several instances in which I had to calm people down once I told them that I was on PrEP because they assumed that my whole lifestyle is changed… One of the regulars that I had previous to going on PrEP decided to stop doing me because he assumed that I would instantly become like a receptacle for every gay plague known to man. So I mean that was kind of an uncomfortable conversation, but I was not ashamed about it.”

Some men described judgemental attitudes from doctors during their initial attempts to get PrEP. More generally, they felt that PrEP’s association with gay sexuality was a structural barrier to broader awareness and access to PrEP.

“If somebody invented an anti-cancer drug, people would say that it is a miracle, regardless of it costing $1000 a month. Because it’s an HIV treatment, there’s still a stigma. Gay men just get it [HIV] because they’re fooling around. That’s not true at all. I think that hurts too.”

Nonetheless, Grace emphasises that his respondents did not present themselves as being overly burdened by stigma or shame. They did not assume a victim narrative and explained that they could manage these negative experiences.

In discussing PrEP, they took pride in being responsible, sexually active gay men who were helping to prevent the spread of HIV. They also celebrated the impact it was having on their sex lives, allowing a ‘return to normality’.

“Frankly, it’s been one of the greatest things of my life. I have absolutely loved it. I have a lot of sex, and I go to the bathhouses a lot, despite my advanced age. I can tell you, sex has never been better. For the first time in my lifetime, it’s taken away the fear from having sex. Sex isn’t meant to be something you’re ashamed of or fearful of. It’s meant to be enjoyable and PrEP has made sex enjoyable for me, which is fantastic… Now that I can have bareback sex again, it’s just fantastic. Sex has been liberating again thanks to PrEP.”

More specifically, PrEP had allowed some participants to challenge stigma or taboos they had in relation to sex with people living with HIV. A man whose primary partner was HIV positive explained that PrEP had empowered him to have better sex with his partner. He explained that although his partner had an undetectable viral load, it was up to his partner to maintain this and he felt more comfortable with a prevention method that he was in control of himself.

Other men said that the use of PrEP could reduce stigma towards men with HIV in the wider community.

“It kind of made me feel good I don’t have to ask guys what their status is and so poz guys don’t have to worry about disclosure or rejection and you know all that stigma stuff, and I like the idea that they have a different experience now that there are so many guys on PrEP because some guys would just — like I don’t ask.”

“These accounts of PrEP use help to shed light on broader stigmas and moral panics around sex and sexuality,” concludes Daniel Grace. “Successfully advocating for broader PrEP access requires that societal and structural stigma surrounding gay sexuality be addressed head on.”

By Roger Pebody

References

Brisson J. Reflections on the history of bareback sex through ethnography: the works of subjectivity and PrEP. Anthropology & Medicine, online ahead of print, 2017. (Abstract).

Grace D et al. The Pre-Exposure Prophylaxis (PrEP)-Stigma Paradox: Learning from Canada’s First Wave of PrEP Users. AIDS Patient Care and STDs, online ahead of print, 2017. (Full text freely available).

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Hepatitis A vaccines effective in high-risk populations during outbreak http://www.eatg.org/news/hepatitis-a-vaccines-effective-in-high-risk-populations-during-outbreak/ Mon, 15 Jan 2018 21:30:13 +0000 http://www.eatg.org/?post_type=news&p=7198 Two-dose hepatitis A vaccination was an effective preventive measure among HIV-positive individuals, including a high study population of men who have sex with men, during an ongoing outbreak of acute HCV, according to recently published data.

“We found that HAV vaccination was highly effective in preventing acute HAV infection during the outbreak, despite the delayed serologic response among HIV-positive individuals,” Kuan-Yin Lin, MD, from the National Taiwan University Hospital, and colleagues wrote. “Our results support HAV serologic screening and vaccination for those at-risk HIV-positive populations in the era of [combination antiretroviral therapy] scale-up.”

Since June 2015, Taiwan has experienced an ongoing outbreak of acute HAV with 1,440 indigenous cases reported as of Sept. 30, 2017. According to the researchers, up to 70% of the reported cases were MSM and up to 60% were HIV-positive patients.

To investigate the serologic response and efficacy of two-dose HAV vaccination among patients with HIV during a large outbreak of acute HAV, the researchers prospectively followed 1,533 adult patients who were seronegative for HAV and positive for HIV from June 1, 2015, to Sept. 30, 2016. Most patients were MSM (94.1%).

Among those enrolled, 1,001 received at least one dose of HAV vaccine and 532 did not. At the end of follow-up, 965 of the vaccinated patients received a second dose and completed 48 weeks of follow-up.

During follow-up, 60 unvaccinated patients and five vaccinated patients acquired HAV. Fifty of the unvaccinated patients had acute HAV and 10 were asymptomatic seroconversion. All patients with acute HAV were MSM and more than 50% had concurrent syphilis.

The incidence rate of acute HAV infection was 3.7 per 1,000 person-years in the vaccinated group and 99.3 per 1,000 person-years in the unvaccinated group.

After multivariate analysis, patients with HIV who received HAV vaccine had significantly reduced risk for HAV infection (HR = 0.04; 95% CI, 0.02-0.1) and acute HAV (HR = 0.05; 95% CI, 0.02-0.14). The prevention rate was 96% for HAV (95% CI, 90-98) and 95% for acute HAV (95% CI, 86-98).

In contrast, acquisition of syphilis during the follow-up correlated with occurrence of acute HAV infection (HR = 3.87; 95% CI, 2.34-6.42) and acute HAV (HR = 4.04; 95% CI, 2.33-7.02).

The seroconversion rate was 7.7% at 4 weeks after the first dose of vaccination, which increased to 21.1% at weeks 5 through 8, 54.2% at weeks 9 through 12, 58.5% at weeks 13 through 16, 64.2% at weeks 17 through 20, and 57.3% between week 21 and the administration of the second dose of HAV vaccine.

Results of an intent-to-treat analysis showed a seroconversion rate of 63.8% at weeks 28 through 36 and 55.4% at week 48, after administration of a second dose. After the researchers applied a last observation carried forward approach, the seroconversion rate was 71.6% at weeks 28 through 36 and 88.4% at week 48. Per-protocol analysis showed a seroconversion rate of 93.7% at weeks 28 through 36 and 94.5% at week 48.

Further adjusted analysis showed an association between seroconversion at weeks 28 through 36 with a younger age (per one-year decrease, OR = 1.08; 95% CI, 1.02-1.12) and undetectable plasma HIV RNA load (PVL) at vaccination (OR = 3.19; 95% CI, 1.32-7.68).

“Despite the delayed and suboptimal serologic response, HAV vaccination was still clinically effective in preventing acute HAV infections,” the researchers concluded. “Improved surrogates of immune status, such as higher CD4 counts, and suppressed PVL, enhanced the immunogenicity to the two-dose vaccine series.”

Lin KY, et al. Hepatol. 2017;doi:10.1002/hep.29780.

By Talitha Bennett

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Serological method could replace molecular for HCV testing http://www.eatg.org/news/serological-method-could-replace-molecular-for-hcv-testing/ Mon, 15 Jan 2018 21:27:33 +0000 http://www.eatg.org/?post_type=news&p=7196 Serologic detection of hepatitis C virus antigen (HCV-Ag) could replace the previous detection standard of molecular HCV-RNA in the era of direct-acting antivirals (DAAs), as DAA effectiveness in treating HCV is not predicted by baseline HCV-RNA levels, and successful treatment is no longer marked by absence of residual HCV-RNA.

“To simplify treatment monitoring, hepatitis C core antigen is emerging as a new tool for diagnosis and treatment monitoring in chronic HCV infection,” wrote principle investigator Pietro Andreone, MD, Department of Medical and Surgical Sciences, University of Bologna, Bologna Italy, and colleagues.

Andreone, and lead author Elisabetta Loggi, PhD, currently at the UOC Patologica Clinica, Fermo, Italy, elaborated on the advantages of applying the serologic testing of HCV-Ag in a statement to MD Magazine.

“Certainly, the main advantage is the general workflow simplification: the automated HCV-Ag testing doesn’t require sophisticated laboratory facilities, specialized technicians, has a much faster turnaround time and lower costs,” Andreone and Loggi said.

Although the HCV-Ag testing has a lower level of sensitivity than HCV-RNA detection, Andreone and Loggi posed the question of whether there is still a need for virological testing with high sensitivity in the DAA era.

The change to DAA treatment from pegylated interferon-based protocols has obviated the need for baseline levels of RNA in order to categorize the patient or to tailor therapy. Also, successful treatment is no longer marked by an absence of HCV-RNA, but by sustained virologic response (SVR).  In addition, there is no longer a “futility/stop treatment” measure from HCV-RNA that is used with DAA regimens.

“A residual viremia during the treatment is currently disregarded, as it does not imply a modification of treatment schedule,” Andreone and Loggi said.

To ascertain the clinical utility of the less costly and more accessible HCV-Ag detection method for monitoring treatment response compared to HCV-RNA, the investigators obtained both values periodically through DAA treatment of 96 consecutive, all-genotype patients with chronic HCV infection presenting to University of Bologna associated outpatient clinics between June 2013 and December 2015.

The investigators found expected patterns. There was a very rapid decrease in HCV-RNA, with negative detection increasing from mean of 16% after 2 weeks, to 55% after 4 weeks, and 99% after 8 weeks of treatment.  The kinetics of HCV-Ag was expectedly different, with 63% negative after 2 weeks and then a slower progression during treatment to 74% after 4 weeks and 83% after 8 weeks.

At the end of treatment, however, all patients except 1 with breakthrough viremia were negative for both HCV-RNA and HCV-Ag.

“Our recent work, in agreement with other similar experiences, showed a general clinical equivalence between HCV-Ag and HCV-RNA monitoring,” Andreone and Loggi said. “Both present a similar kinetic disappearance from serum during DAA treatment, despite the lower sensitivity of HCV-Ag, which does not seem to limit the performance of the test.”

The researchers opined that HCV-Ag is a strong candidate for simplified, cost-saving virological testing for HCV, and should be implemented “both as index of viral replication and to assess the response to pharmacological treatment.”

The study, “Monitoring the treatment of hepatitis C with directly acting antivirals by serological and molecular methods,” was published online in PLOS one in November.

By Kenneth Bender

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Halving HIV incidence in US requires ‘ambitious’ goals, researchers say http://www.eatg.org/news/halving-hiv-incidence-in-us-requires-ambitious-goals-researchers-say/ Mon, 15 Jan 2018 21:25:56 +0000 http://www.eatg.org/?post_type=news&p=7200 To cut HIV incidence in half by 2025, treatment programs need to retain at least 95% of patients each year and re-engage people living with HIV within a year and a half, study data showed.

“There are currently an estimated 1.1 million persons aged 13 [years] and older living with HIV (PLWH) in the United States, with some estimates suggesting that less than 50% are retained in care,” Maunank Shah, MD, PhD, assistant professor at Johns Hopkins University School of Medicine, and colleagues wrote. “Despite improvements in ART and evidence for ‘treatment as prevention’ with guidance for early ART initiation, incidence of HIV has declined at a slow rate and remains between 36,000 to 39,000 new HIV infections per year. Among the challenges is an imperfect HIV care continuum, in which current national estimates suggest that suboptimal numbers of PLWH are virologically suppressed, representing missed opportunities for averting ongoing HIV transmission.”

Among its goals, the U.S. National HIV/AIDS Strategy aims to reduce 25% of new HIV infections by 2020. However, Shah and colleagues said there is a “paucity of useable program-level benchmarks tied to population-level epidemiologic goals.” They sought to define “tangible benchmarks” for annual rates along the HIV care continuum that can result in significant reductions in HIV incidence in the U.S. In a modeling study, they generated approximately 100,000 simulations to determine the annual rates of screening, retention and re-engagement of care, and the percentage of PLWH linked to care that is needed to achieve a 50% reduction in HIV incidence by 2025.

Seven percent of all simulations achieved a 50% reduction in HIV incidence, the researchers reported. Even when the models included high rates of care re-engagement, it was not possible for any simulation to achieve the target incidence if more than 20% of patients disengaged from care. However, when the rate of retention was 95% and PLWH who had disengaged from care re-engaged within a mean of 1.5 years, there was roughly a 90% chance of cutting HIV incidence in half by 2025.

“These goals for retention and re-engagement rates are ambitious, and future research should focus on their feasibility (ie, specific intervention efficacy and costs) and identifying evidence-based effective strategies to achieve such targets, while also emphasizing the need for a comprehensive approach including scale-up of prevention and accounting for potential changes in transmission over the next decade,” the researchers wrote. “As HIV care programs move forward, our model suggests that efforts, resources and priorities must be focused on retaining almost all PLWH in care and frequently re-engaging those out of care to reduce HIV incidence in the U.S. over the next decade.”

Perry A, et al. Open Forum Infect Dis. 2018;doi:10.1093/ofid/ofy008.

By Andy Polhamus

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New model for uncovering true HIV mortality rates in Zambia http://www.eatg.org/news/new-model-for-uncovering-true-hiv-mortality-rates-in-zambia/ Mon, 15 Jan 2018 21:10:04 +0000 http://www.eatg.org/?post_type=news&p=7189 A new study that seeks to better ascertain HIV mortality rates in Zambia could provide a model for improved national and regional surveillance approaches, and ultimately, more effective HIV treatment strategies.

Survival represents the most important indicator of successful HIV treatment, according to the researchers. According to UNAIDS, AIDS-related deaths have fallen by 50 percent since 2005 — largely due to the successes of national HIV programs with support from PEPFAR and the Global Fund. Yet, because routine monitoring and evaluation fails to systematically capture most deaths, it can be challenging to accurately assess the impact of HIV services and to identify where improvement is most needed, the researchers say.

The Better Information for Health in Zambia (“BetterInfo”) study begins to examine HIV survival rates in Zambia. Published January 12 in PLOS Medicine, the work was conducted by a team of researchers co-led by Charles Holmes, MD, MPH, faculty co-director of Georgetown University Medical Center’s Center for Global Health and Quality, and visiting associate professor at Georgetown’s School of Medicine. Holmes led the work along with Izukanji Sikazwe, MBChB, MPH, chief executive officer of the Centre for Infectious Research in Zambia (CIDRZ) and Elvin Geng, MD, MPH, of the University of California, San Francisco. Holmes, who previously led CIDRZ, also serves as associate professor of international health at the Johns Hopkins University Bloomberg School of Public Health and associate professor of medicine at the Johns Hopkins University School of Medicine.

The research was conducted in Zambia through a partnership with CIDRZ and the Zambian Ministry of Health, in close collaboration with numerous local and global academic centers and researchers.

The research group set out to provide a more accurate representation of site- and regional-level mortality among people on HIV therapy in Zambia by characterizing the extent of under-reporting of mortality and the variability in data collection and use, and to assess the broader impact this might have on treatment programs and outcomes.

The group applied a multistage sampling-based approach — which they say is a novel methodology in this context — to obtain regionally representative mortality estimates in four Zambian provinces (Lusaka, Southern, Eastern, and Western). The estimates were also sufficiently precise to quantify variation in death rates among clinic sites.

They looked at a sample population of more than 160,000 patients who had visited government-operated HIV treatment sites in these provinces to determine: the magnitude of deaths of those who were taking antiretroviral therapy (ART); when deaths occurred; which groups are at highest risk of death; and whether these factors differ by region, facility, or other variables.

They also traced patients who were lost to follow-up to ascertain their status, and then used this information to create a corrected regional survival estimate as well as corrected site-specific mortality estimates.

The BetterInfo study concluded that mortality is substantially underreported in routine provincial program data — by as much as three- to nine-fold — among HIV-infected individuals starting ART, leading to a change in the ranking of provinces by mortality rates.

At the site-level, “corrected” mortality rates were found to be up to 23-fold higher among those on ART. The study also found unexpectedly high variability from site to site in reported mortality rates, ranging from less than 1 death per 100 person-years to up to 13.4 deaths per 100 person years over a two-year period.

“Even as we strive to reduce new HIV infections and end the HIV pandemic as a public health threat, we must not lose sight of premature deaths occurring amongst people living with HIV who are on treatment,” Holmes says. “HIV treatment is not a ‘set it and forget it’ proposition — deaths often occur outside of the health system and are therefore ‘silent’ events that are unknown to those providing or managing care.

“We believe our scalable approach, which builds on and extends earlier sampling methods, provides actionable data to clinic, provincial and national decision-makers to ensure the HIV program in Zambia is able to become more patient-centered and impactful,” he says.

Based on the findings, certain prevailing assumptions that underlie HIV programs may need to be reexamined. For example, the researchers say it has been assumed that most patients on treatment for longer periods of time will be more stable than those just starting treatment. However, the study data suggest that time on therapy alone may not be a reliable marker of stability, a finding that will have implications for delivery strategies recommending less health system interaction for patients considered clinically stable.

In addition, approximately 50 percent of deaths among those newly starting ART occurred relatively shortly after a recent clinic visit, suggesting even greater need for attention to diagnostic services and clinical vigilance for potential co-existing illnesses.

Overall, the authors seek to encourage national- and global-level policy makers to investigate and address the root causes of underestimated and highly variable mortality rates so they can refocus their quality improvement efforts and strengthen HIV programs.

“These data from the BetterInfo study have provided new targets for quality improvement efforts, and we look forward to further evidence as it emerges that will enable us to support the strongest possible national HIV program in Zambia,” says CIDRZ’s Sikazwe. “We recommend that others consider the application of similar large-scale surveillance methodologies in order to better understand their program outcomes, and we are excited to facilitate broader adoption through the forthcoming release of a “BetterInfo” toolkit and other materials.”

Holmes adds, “We believe our study also highlights the critical need for investments in vital status registries and data systems to enable better visibility into patient outcomes. These investments are critical not just for the HIV response, but for broader efforts to combat chronic conditions such non-communicable diseases and achieve universal health coverage.”

Journal Reference:

  1. Charles B. Holmes, Izukanji Sikazwe, Kombatende Sikombe, Ingrid Eshun-Wilson, Nancy Czaicki, Laura K. Beres, Njekwa Mukamba, Sandra Simbeza, Carolyn Bolton Moore, Cardinal Hantuba, Peter Mwaba, Caroline Phiri, Nancy Padian, David V. Glidden, Elvin Geng. Estimated mortality on HIV treatment among active patients and patients lost to follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based survey. PLOS Medicine, 2018; 15 (1): e1002489 DOI: 10.1371/journal.pmed.1002489
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Report highlights the need to clean the conversation around drug use http://www.eatg.org/news/report-highlights-the-need-to-clean-the-conversation-around-drug-use/ Thu, 11 Jan 2018 22:59:18 +0000 http://www.eatg.org/?post_type=news&p=7180 Skewed perceptions of drugs and people who use them negatively affect both health and health care by feeding into harmful prohibitionist policies and sometimes directly affecting clinical care, according to a new international report that aims to counter such prejudices.

The report, titled The World Drug PERCEPTION Problem, was released on Tuesday by the Global Commission on Drug Policy. The 25-member delegation includes 12 former heads of states or government, a former secretary general of the United Nations and three Nobel Prize laureates.

Ruth Dreifuss, chair of the commission and former president of Switzerland, said the stigmatization of people who use drugs leads to discrimination and supports “regressive drug laws based on moral judgment.”

“Whether you think of someone and refer to them as a person who uses drugs or a ‘junkie’ makes a huge difference in how you and society will treat them,” Ms. Dreifuss said in a statement. “The vicious cycle, which has been fuelled for decades, must be broken.”

The report comes as North America grapples with an overdose crisis brought on by illicit fentanyl. Canada’s 2017 death toll from opioid-related overdoses is expected to surpass 4,000, with roughly a third of those deaths in British Columbia.

Amid media reports on the escalating crisis and impassioned debates about possible solutions, advocates have cautioned against using language that stigmatizes drug use or portrays people who use drugs as morally flawed or inferior. Rather, language should be “people-first” and reflect the medical nature of substance use. “Person with a substance use disorder” should be used over “addict” or “junkie” for example and “supervised consumption site” over “fix site” or “shooting gallery.”

(The American Press Stylebook, a grammar and usage guide for journalists in the United States, last year issued an update recommending against using words such as alcoholic, addict, user and abuser unless they are in quotations. Instead, the new guide recommends phrasing such as “he was addicted,” or “people with alcoholism.”)

The report noted that stigmatization can have a direct impact on clinical care, citing a U.S. study in which mental-health clinicians were given identical case studies about people in court-ordered drug-treatment programs.

“The individual was either referred to as a ‘substance abuser’ or ‘someone with a substance use disorder,'” the report stated. “The trained mental health professionals who read about an ‘abuser’ were more likely to believe that the individual in question was personally culpable for their situation and that punitive measures should be taken.”

Such negative perceptions of drugs and drug use can also feed into policies such as mandatory minimum sentencing on petty drug crimes and compulsory treatment programs that are not only ineffective but violate human rights, the report stated.

Jane Buxton, harm reduction leader at the BC Centre for Disease control, issued a report last year encouraging the use of non-stigmatizing language when describing substance-use disorders, addiction and people who use drugs.

Her report also highlighted self-stigma – shame, negative self-evaluative thoughts and fear – that can develop when a person who uses drugs identifies with a stigmatized group.

“Those who experience self-stigma are less likely to seek employment, find it difficult to develop intimate contacts and are more likely to avoid treatment,” Dr. Buxton’s report stated. “When [people who use drugs] adopt [stigmatizing] terms for themselves they are likely to experience self-stigma and ‘accept’ that they cannot recover.”

Karen Ward, a drug-policy advocate and former board member with the Vancouver Area Network of Drug Users, has mulled the effect of language on people’s perception of drug use. She has floated the idea of relabeling B.C.’s overdose crisis as a poisoning crisis to reflect the fact that most people are not choosing to use lethal amounts of fentanyl.

“It was something happening to people,” Ms. Ward said. “It wasn’t a dose that people were doing too much of; it was something that was happening to them and they didn’t have any control over it.”

The Global Commission’s report concludes with six recommendations. They include for policy makers to strive to change perceptions of drugs and people who use them by providing reliable and consistent information; and for United Nations member states to review language while negotiating international political agreements on drug control.

By Jonathan Hayward

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Study suggests many gay and bisexual men are skeptical, but attitudes are on the rise http://www.eatg.org/news/study-suggests-many-gay-and-bisexual-men-are-skeptical-but-attitudes-are-on-the-rise/ Thu, 11 Jan 2018 22:55:14 +0000 http://www.eatg.org/?post_type=news&p=7179 Dr. Jonathon Rendina, an Assistant Professor at Hunter College and Director of Quantitative Methods at Hunter’s Center for HIV Educational Studies & Training, and Dr. Jeffrey Parsons, Distinguished Professor at Hunter and Director of CHEST, have published a new paper in the Journal of the International AIDS Society focused on gay and bisexual men’s perceptions of the HIV treatment-as-prevention message, “Undetectable = Untransmittable.” Numerous well-controlled trials have recently demonstrated that there is effectively no risk of HIV transmission during sex with a partner who has a sustained, undetectable viral load. This notion, that HIV treatment can lead to HIV prevention, has been captured with the #UequalsU slogan popularized by Bruce Richman and the Prevention Access Campaign, of which he is Executive Director, and has gained growing popularity and endorsements, including the U.S. Centers for Disease Control and Prevention (CDC). The Hunter CHEST study sought to examine how accurate gay and bisexual men perceive this message to be by surveying more than 12,000 men across the United States in the summer of 2017.

“Some studies have examined beliefs about treatment-as-prevention generally, though they have largely been done outside of the U.S. and weren’t focused on any specific message,” said Dr. Rendina, lead author of the paper. Overall, the message was perceived to be accurate by 70% of men who were HIV-positive and 36% of men who were HIV-negative or unsure of their HIV status—though there is some room for improvement, these rates suggest there have been increases since earlier studies. “We found that HIV-negative and unknown guys were more likely to believe the message was accurate if they got tested for HIV more regularly and if they were taking pre-exposure prophylaxis (PrEP), suggesting these prevention services may be a great way to gain a captive audience to provide more information about treatment-as-prevention.”

In addition to promoting HIV knowledge, one goal of the message is to help reduce HIV stigma. Mr. Richman noted, “This study underscores the great need for further targeted educational and dissemination strategies and provides data that will be immensely valuable as we work with our partners to scale up campaigns to prevent new transmissions and reduce HIV stigma.” Among HIV-positive men, reporting a detectable viral load was associated with believing the message was less accurate. Dr. Rendina added, “What we may be seeing is that some guys who aren’t able to maintain a sustained undetectable viral load either have lower levels of knowledge potentially due to being less well-retained in care or that they may feel left out of the message and concerned it will lead to additional stigma placed on them.” He continued, “There is great promise for the message to reduce HIV stigma, but at the same we need to make sure we don’t end up marginalizing or stigmatizing those who struggle with keeping their viral loads undetectable.”

Among men with and without HIV, believing the message was more accurate was associated with having had condomless anal sex with a partner of a different HIV status. Dr. Parsons noted, “This suggests that men who understand the scientific evidence, now endorsed by the CDC, that Undetectable = Untransmittable feel more comfortable having condomless sex when a positive partner is virally suppressed. Because they know that treatment-as prevention is effective—as with other forms of biomedical prevention, like PrEP, it’s giving men more options regarding their sexual health that emphasize autonomy and sexual pleasure. The message of ‘use a condom every time’ is now outdated and limiting.” Strategies such as regular viral load monitoring, efforts to maintain medication adherence, routine screening for sexually transmitted infections, better access to PrEP, and promoting communication about biomedical prevention with sexual partners can be helpful in conjunction with treatment-as-prevention to continue curbing the HIV epidemic and averting new epidemics among other sexually transmitted infections.

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About the study: The results of the study, entitled, “Factors associated with perceived accuracy of the Undetectable = Untransmittable slogan among men who have sex with men: Implications for messaging scale-up and implementation” (doi: 10.1002/jia2.25055) by H. Jonathon Rendina and Jeffrey T. Parsons will be published in an upcoming issue of JIAS.

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NIH study supports use of short-term HIV treatment interruption in clinical trials http://www.eatg.org/news/nih-study-supports-use-of-short-term-hiv-treatment-interruption-in-clinical-trials/ Thu, 11 Jan 2018 22:50:45 +0000 http://www.eatg.org/?post_type=news&p=7178 Findings may aid design of trials to assess strategies to control HIV without drugs.

A short-term pause in HIV treatment during a carefully monitored clinical trial does not lead to lasting expansion of the HIV reservoir nor cause irreversible damage to the immune system, new findings suggest.

Antiretroviral therapy (ART) benefits the health of people living with HIV, prolongs their lives and prevents transmission of the virus to others. If taken daily as directed, ART can reduce viral load — the amount of HIV in the blood — to levels that are undetectable with standard tests. However, the virus remains dormant in a small number of immune cells, and people living with HIV must take ART daily to keep the virus suppressed. If a person with ART-suppressed HIV stops taking medication, viral load will almost invariably rebound to high levels.

Researchers are working to develop therapeutic strategies to induce sustained ART-free remission — the absence of viral rebound following discontinuation of ART. Clinical trials to assess the efficacy of such experimental therapies may require participants to temporarily stop taking ART, an approach known as analytical treatment interruption, or ATI.

In the current study, researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, sought to better understand the immunologic and virologic effects of ATI. They analyzed blood samples from 10 volunteers who had participated in a clinical trial evaluating whether infusions of a broadly neutralizing antibody could control HIV in the absence of ART. During the trial, participants temporarily stopped taking ART. The 10 participants evaluated in the current study subsequently experienced viral rebound and resumed ART 22 to 115 days after stopping. While treatment was paused, the participants’ HIV reservoirs expanded along with increases in viral load, and researchers observed abnormalities in the participants’ immune cells. However, six to 12 months after the participants resumed ART, the size of the HIV reservoirs and the immune parameters returned to levels observed prior to ATI.

The findings support the use of ATI in clinical trials to evaluate the efficacy of therapeutic strategies aimed at achieving sustained ART-free remission, the authors conclude. However, larger studies that do not involve any interventional drugs are needed to confirm and expand on these results. The NIAID investigators currently are conducting a clinical trial to monitor the impacts of short-term ATI on a variety of immunologic and virologic parameters in people living with HIV.

Article

KE Clarridge, J Blazkova et al. Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals. PLOS Pathogens DOI: 10.1371/journal.ppat.1006792 (2018).

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Withdrawing Depo-Provera contraceptives would result in more lives lost than HIV infections prevented http://www.eatg.org/news/withdrawing-depo-provera-contraceptives-would-result-in-more-lives-lost-than-hiv-infections-prevented/ Thu, 11 Jan 2018 22:25:47 +0000 http://www.eatg.org/?post_type=news&p=7177

Even if Depo-Provera and other contraceptive injections raise the risk of HIV infection, withdrawing them from use in African countries would greatly increase maternal mortality, a modelling study has shown. The loss of life due to pregnancy complications and unsafe abortions would far outweigh the number of HIV infections prevented, according to the study published in the December issue of Global Health: Science and Practice.

Observational studies have produced conflicting evidence about a possible link between hormonal contraception – especially depot medroxyprogesterone acetate (DMPA, often marketed as Depo-Provera), a long-acting progesterone-only injectable – and women’s risk of HIV infection. It’s not clear whether an apparent increase in HIV infections reflects a real biological effect of the contraceptive or if the results are skewed by factors which the researchers haven’t been able to fully take into account, particularly differences in the sexual behaviour of contraceptive users and non-users.

Pooling the results of these studies, a recent meta-analysis found that HIV-negative women using DMPA may be at increased risk of acquiring HIV, with a pooled hazard ratio of 1.4 (95% confidence interval 1.2-1.6). More definitive data is likely to come from ECHO, an ongoing randomised clinical trial, which may report results in 2019.

In the meantime, the World Health Organization recommends that DMPA and other long-acting progestogen-only injectables should remain accessible to women at high risk of HIV, “because the advantages of these methods generally outweigh the possible increased risk of HIV acquisition”. However, women at high risk of HIV who choose to use these methods should be counselled about the possible increased risk of HIV and how to reduce this risk.

The study

The recently published modelling study sheds light on the balance of benefits and risks with the use of injectable contraceptives. It focuses on nine countries in sub-Saharan Africa, the world region which has both the greatest burden of HIV and of maternal mortality. In Africa, for every 200 live births, one woman dies during pregnancy, during childbirth or following an abortion. Access to services providing modern contraceptives is poor; around a third of pregnancies in Africa are unintended; and over 98% of abortions are unsafe.

The researchers used a decision-analytic model to assess the potential impact of changing family planning provision (removing DMPA / Depo-Provera and other progesterone-only injectables) in Burkina Faso, Chad, Democratic Republic of the Congo, Kenya, Senegal, South Africa, Malawi, Tanzania, and Uganda. The countries chosen reflect variations in maternal mortality, contraceptive mix and uptake, and HIV incidence. They are the countries, say the researchers, “where the balance between benefit and harm is most nuanced”.

For each country, the model incorporated data on HIV incidence, access to HIV treatment, usage of different contraceptive methods, maternal mortality and life expectancy. Country-by-country variation in these factors affected the results.

In line with the meta-analysis, the researchers assumed that injectables are associated with a 1.4 increased risk of acquiring HIV.

The population of focus was women of reproductive age, who did not have HIV and were not planning a pregnancy. The main analysis considered the number of life-years lost or gained. Clearly, a maternal death would be an immediate loss of life. An HIV infection with access to HIV treatment was assumed to result in a 25% reduction in life expectancy. An HIV infection without HIV treatment would result in a 75% reduction in life expectancy.

However, it should be noted that this focus on deaths could obscure attention from the wider impact of poor health. Both living with HIV and having complications in pregnancy could have a long-term impact on quality of life. Nonetheless, the researchers did not use a measure which would reflect this, such as quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs).

Results

The main scenario considered was DMPA being withdrawn, without replacement by equally effective reversible contraceptive methods. In this scenario, considering the nine countries together, for every 100,000 women, there would be 9000 life-years lost. There was variation between countries, but in all countries the impact would be negative.

For example, in Kenya, for every 100,000 women, there would be 6600 life-years lost. This is largely due to there being an additional 341 maternal deaths per 100,000. While there would be 49 fewer HIV infections per 100,000 women, the decreased use of contraception by women living with HIV would result in 35 additional HIV infections in infants per 100,000 women, so overall there would only be 14 fewer HIV infections a year per 100,000.

Even in South Africa – a country with a very high HIV incidence and relatively low maternal mortality – for every 100,000 women, there would be 1000 life-years lost. There would be 146 additional maternal deaths per 100,000 women. The 117 fewer HIV infections per 100,000 women would be negated by 114 additional HIV infections in infants per 100,000 women.

An additional scenario considered the effect of replacing DMPA with usage of an equally effective contraceptive, such as an intra-uterine device (IUD) or implant. This analysis found that in all countries apart from South Africa, an unrealistically large proportion of women (over 93%) would need to switch to the new method for there not to be a negative impact on life-years. The researchers say that in any change of family planning provision, significant efforts need to be made to ensure that women find alternative contraceptive methods accessible and acceptable.

“Our model found that removal of POIs [progesterone-only injectables] from the market without effective and acceptable contraception replacement would have a net negative effect on maternal health, life expectancy, and mortality, and this persisted under a variety of modeled scenarios,” the authors conclude. “Policy and programmatic decisions about the role of POIs in family planning programs must therefore be made cautiously, with continued recognition of the interconnectedness of these health issues.”

By Roger Pebody

Reference

Rodriguez MI et al. Re-evaluating the possible increased risk of HIV acquisition with progestin-only injectables versus maternal mortality and life expectancy in Africa: a decision analysis. Global Health: Science and Practice. 2017;5(4):581-591. (Full text freely available.)

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UN publication urges comprehensive approach to sexuality education http://www.eatg.org/news/un-publication-urges-comprehensive-approach-to-sexuality-education/ Wed, 10 Jan 2018 22:59:04 +0000 http://www.eatg.org/?post_type=news&p=7173

A fully updated International Technical Guidance on Sexuality Education published by UNESCO advocates quality comprehensive sexuality education (CSE) to promote health and well-being, respect for human rights and gender equality, and empowers children and young people to lead healthy, safe and productive lives.

The Technical Guidance is designed to facilitate countries’ effort to provide children and young people with accurate and age-appropriate knowledge, attitudes and skills to help them build up positive relationships. It was produced in collaboration with UNAIDS, United Nations Population Fund (UNFPA), United Nations Children’s Fund (UNICEF), UN Women, and the World Health Organization (WHO).

“The International Technical Guidance on Sexuality Education benefits from a new review of the current evidence, and reaffirms the position of sexuality education within a framework of human rights and gender equality,” says UNESCO Director-General Audrey Azoulay. “It promotes structured learning about sex and relationships in a manner that is positive, affirming, and centred on the best interest of the young person. By outlining the essential components of effective sexuality education programmes, the Guidance enables national authorities to design comprehensive curricula that will have a positive impact on young people’s health and well-being.”

Based on a review of the current status of sexuality education around the world and drawing on best practices in the various regions, the Guidance demonstrates that sexuality education has positive effects on young people, allowing them to become more responsible in their attitudes and behaviour with regard to sexual and reproductive health.

The publication shows that sexuality education, in or out of schools, does not increase sexual activity, sexual risk-taking behavior, or STI/HIV infection rates. It also presents evidence showing that abstinence-only programmes fail to prevent early sexual initiation, or reduce the frequency of sex and number of partners among the young.

The publication identifies an urgent need for high quality, curriculum-based CSE, which is still unavailable in all too many countries around the world due to persistent resistance, depriving all too many young people of guidance about physical, social and emotional development as they transition from childhood to adulthood.

The Guidance advocates CSE to help young people overcome the challenges posed by sexual and reproductive health issues, which are particularly difficult during puberty. These challenges include access to contraception, early pregnancy, gender-based violence, sexually transmitted infections (STIs) and HIV and AIDS. They are exacerbated by the internet, where a great deal of material of varying quality relating to sexuality abounds, and by the pressure of cyberbullying, which is on the rise.

Conceived to help education, health and other relevant authorities develop and implement sexuality education programmes and materials, the publication recognizes the need to adapt sexuality education to the diverse of contexts in which it is taught. But the Guidance also reaffirms the central relationship between sexuality education and human rights, notably gender equality, in all contexts.

The Technical Guidance clarifies the definition and content of comprehensive sexuality education, outlining key concepts, topics and learning objectives which should guide the development of locally-adapted curricula for learners aged 5 – 18+. These include:

  • Relationships;
  • Values, rights, culture and sexuality;
  • Understanding gender;
  • Violence and staying safe;
  • Skills for health and well-being;
  • The human body and development;
  • Sexuality and sexual behavior; and
  • Sexual and reproductive health.

The Technical Guidance also includes recommendations for all stages of CSE programme development, from planning and delivery, to monitoring, evaluation and scale up.

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London joins Fast-Track Cities initiative to reduce new HIV infections http://www.eatg.org/news/london-joins-fast-track-cities-initiative-to-reduce-new-hiv-infections/ Wed, 10 Jan 2018 22:55:08 +0000 http://www.eatg.org/?post_type=news&p=7175 Mayor of London, Sadiq Khan, joins Fast-Track Cities initiative as part of a major push to reduce the rate of new HIV infections and eliminate stigma in London – aiming to end new HIV infections by 2030

Sadiq Khan signed the historic pledge today alongside partners from London Councils, Public Health England and NHS England

Read the full announcement here.

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An inside look at Ukraine’s terrifying TB outbreak http://www.eatg.org/news/an-inside-look-at-ukraines-terrifying-tb-outbreak/ Wed, 10 Jan 2018 22:54:48 +0000 http://www.eatg.org/?post_type=news&p=7166 Strains of drug-resistant tuberculosis are spreading across Ukraine, where armed conflict and market misgivings are making a bad situation even worse.

KRAMATORSK, 3 January 2018 — My car turns off the multi-lane main street, filled with 50-year-old Ladas and Soviet-style trucks, onto a road full of potholes and scrub. Beyond that is the Narkologia Dispenseria, a hospital somewhat hidden in a park in Kramatorsk, a city of more than 150,000 inhabitants in eastern Ukraine. With its crumbling, mint green walls it looks more like more of a bunker than a healthcare facility. Plaster falls off the walls and staircases inside. Neon lights cast a pale glow in the corridors.

The Dispenseria is like an outpost of the Ukrainian health care system, and Natalia Nikolaeva is the border guard. In silver shoes, the doctor keeps watch behind a desk on the ground floor. A pearl necklace embellishes her white laboratory coat. For about 100 euros a month, Nikolaeva stands here every morning, sorting methadone into cups and dispensing the pills to patients, who at 8 a.m. are already standing in a line to alleviate their withdrawal symptoms.

The clinic’s 85 admitted patients have been addicts for many years, mostly of opiates. Every third person is infected with HIV. The Dispenseria provides treatment for the virus as well. The infected receive life-saving antiretroviral medications that suppress the HIV. This group, though, “is only the tip of the iceberg,” says Nikolaeva.

The wait list to be admitted into the opioid substitution program is long, and there are many others, presumably, who need treatment but haven’t even sought it out. Staff at the Dispenseria estimate that some 10,000 people in Kramatorsk alone are addicted to hard drugs. The abundance of narcotics has, in turn, spurred disease in Ukraine, where, next to Russia, the HIV rate is the highest in all of eastern Europe and Central Asia. Tuberculosis, TB, has also returned under these conditions. But unlike HIV, treatment against TB has mostly failed.

Fatal mistake

Treating even a weak-strain of tuberculosis is an ordeal. Patients must take medication daily for six months, usually with intense side effects. As of late, however, doctors have observed that for every fourth new tuberculosis infection, most antibiotics don’t work at all. These so-called multi-drug resistant (MDR) bacteria strains have developed resistance against several agents. Treatment of MDR-TB is complicated and expensive; therapy lasts up to 20 months. The pathogen is especially aggressive in people with weakened immune systems — HIV patients, for example,

“Tuberculosis is now the primary reason why HIV-positive people die,” says Dmytro Sherembey of the Ukrainian HIV organization Network 100 Percent Life.

Because people with tuberculosis are so poorly treated, resistance is on the rise. In Ukraine, the infected are isolated in hospital wards. This scares many of the them because they aren’t able to go to work for several months and therefore many end up in poverty. And so they avoid treatment, or else abandon therapy prematurely because they feel healthy again — a fatal mistake. Ending treatment gives the remaining bacteria an opportunity to adapt to the agents and develop resistance. In due time, the disease comes back, stronger than before.

“Then, from a treatable tuberculosis comes a resistant, and potentially even an extensively drug-resistant tuberculosis,” says Sherembey. With the most aggressive from, known as XDR-TB, chances of recovery are only minimal. Some 1,200 cases of extensively drug-resistant bacteria are currently recorded in Ukraine. Only India has higher numbers. The root cause for this development, Sherembey believes, is the miserable state of infection control in clinics and prisons.

That the pathogen has spread so rapidly in the region also has a political basis. For almost five years, pro-Russian separatists have controlled eastern Ukraine. Some 10,000 people have died in the conflict, and there are still occasional skirmishes. In Kramatorsk, army vehicles loaded with heavy weapons and soldiers depart in the direction of the “contact line” with the separatists, a few dozen kilometers to the southeast. Health refugees have streamed in the other direction for years.

Dmitri Volkov is one of the them. He comes from a small city east of the disputed border. After the separatists took over, doctors somehow kept the local program for addicts and HIV patients running for a year. “From one day to the next, there was no medication,” says Volkov. Instead, there was constant bombing. “I was very scared.” The refugee now lives in Kramatorsk. Another patient tells me that he travels from one side to the other every day. Today, his commute lasted four hours. He was held up at the border crossing for two hours. Thousands have fled for health reasons.

It’s difficult to judge how the situation looks for those who stayed. Two years ago, Doctors Without Borders discontinued its tuberculosis program in the self-declared People’s Republic of Donetsk. A committee of separatists had accused the organization of espionage and revoked its accreditation. The organization withdrew in protest.

There are no published numbers on the spread of tuberculosis or HIV in Luhansk, the second self-declared people’s republic. Aid agencies in Kiev have reported on the bad conditions along the border, where both sides stand face-to-face. Because women there hardly ever have legal ways to earn a living, an enormous, unregulated and unhygienic market for prostitution has developed.

Market failure

The conflict between Russia and Ukraine has had an especially negative impact on the treatment of XDR-TB, the most dangerous form of tuberculosis. The pathogen is evolving. And yet to treat it, doctors are using the same antibiotics they did 50 years ago. Recently, two new medications came on the market, Bedaquiline and Delamanid. And they’ve proven effective in some cases. When physicians from Doctors Without Borders recently healed a patient of extensively drug-resistant TB bacteria in Belarus, the organization hailed it as a milestone.

In Ukraine, though, the drugs are unavailable for political reasons. Janssen and Otsuka, the manufacturers, licensed the sale of the medications in Ukraine to the Russian pharmaceutical companies Pharmstandard and R-Pharm. But since the conflict’s outbreak, Russians are no longer allowed to do business in Ukraine. The effect is that physicians do not have access to the medications. The Japanese firm Otsuka is supposedly working on the problem. Next year, it wants to offer the medication separately on the Ukrainian market.

But the problem is larger than two, single antibiotics. “There is a huge shortage of new medications against TB,” says physician Yuri Varchenko in Kiev. For pharmaceutical companies, the disease is financially not interesting enough for them to research it. This might seem paradoxical given the size of the epidemic. After all, 10 million people worldwide contract TB annually, and 1.7 million die. And yet, with the exception of eastern Europe and Russia, the sick live in the slums of India, Pakistan, and southern Africa. In other words, they are hardly a solvent clientele.

“The market just isn’t interested in this issue,” says Varchenko. With this market failure comes a great deal of ignorance: As early as the mid-20th century, many epidemiologists falsely maintained that the pathogen was as good as eradicated.

“We need earlier diagnoses, new drugs, and a better vaccine,” says Stefan Kaufmann, who, as director of the Max Planck Institute (MPI) for Infection Biology, has researched TB for decades. Only then can TB be stemmed. Kaufmann estimates that annually, 2 billion euros alone would be needed for research. That’s four times more than today.

A new vaccine is urgently required. The vaccine in use today, developed decades ago, no longer offers protection. Kaufmann himself has recently launched a three-phase study in India. There, beginning next year, 2,000 adults are set to be immunized in order to test a new agent developed by MPI. This is because the sickness reappears in up to 15% of people who are already considered healed, often in a tougher form.

“Precisely these types of people are now being inoculated,” says Kaufmann. The MPI director expects results by the end of 2019. “It would be the first successful vaccine” — but only if everything goes as planned.

By Christoph Behrens

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Stop TB and Global Fund deepen cooperation to find missing cases of TB http://www.eatg.org/news/stop-tb-and-global-fund-deepen-cooperation-to-find-missing-cases-of-tb-2/ Wed, 10 Jan 2018 22:53:07 +0000 http://www.eatg.org/?post_type=news&p=7163 GENEVA, 18 December 2017 – The Stop TB Partnership and the Global Fund today signed a new collaboration agreement to contribute towards the goal of finding and treating an additional 1.5 million people with tuberculosis who are currently missed by health systems.

Under the TB Strategic Initiative, the Stop TB Partnership will work with national TB programs and partners in 13 countries, providing technical support through a combination of innovative approaches and best practices to remove barriers to accessing TB services, with a particular focus on key populations and vulnerable groups.

In 2016, 10.4 million people got sick with TB, an entirely preventable and curable disease. Only 6.3 million were detected and officially notified, leaving a gap of 4.1 million people who were “missed” by health systems after failing to be diagnosed, treated or reported. The result is many will die or continue to be sick and transmit the disease or, if treated with improper drugs, contribute to the growing menace of drug resistance.

The agreement is part of the TB Catalytic Investment initiative, an ambitious effort that brings together WHO, the Stop TB Partnership, the Global Fund and other implementing partners to stop the spread of TB and reach the global goal of ending TB as an epidemic by 2030.

Lucica Ditiu, Executive Director of the Stop TB Partnership, said the agreement will provide much-needed impetus to help countries begin closing gaps by finding cases of both drug-susceptible TB and drug-resistant TB.

“We have set an ambitious target of finding and treating an additional 1.5 million missing cases of TB by 2019. This agreement allows us to work shoulder-to-shoulder with the Global Fund, implementers and health partners in ensuring we reach our objective,” Dr. Ditiu said.

“Missing TB cases including drug-resistant TB are major challenges in fighting the disease, and pose a serious threat to global health security,” said Marijke Wijnroks, Interim Executive Director of the Global Fund.

“Only through partnership and smart investments will we achieve the global goal of ending TB as an epidemic,” said Dr. Wijnroks.

The TB Catalytic Investment initiative includes US$115 million in matching funds designed to support country-led programs; a US$65 million multi-country TB investment for programs focused on migrant and cross-border issues, the mining sector, refugees, improved laboratory services, and transition to domestically funded health programs; and the US$10 million TB Strategic Initiative. The 13 countries that are part of the TB Catalytic Investment initiative are Bangladesh, Democratic Republic of Congo, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, South Africa, Tanzania, Ukraine, Kenya, Mozambique and India.

Some key interventions of the TB Strategic Initiative include carrying out gender and legal assessments to help remove barriers to accessing TB services, developing a handbook on best practices and innovative case-finding activities, and providing technical assistance to help countries implement Global Fund-supported interventions.

Deaths from drug-resistant TB – when tuberculosis bacteria do not respond to first-line TB drugs – now account for about one-third of all antimicrobial resistance deaths worldwide. The rise of antimicrobial resistance coincides with the growth of TB. Despite steady progress since 1990, the disease killed 1.7 million people in 2016 (including 400,000 HIV-positive people), surpassing HIV as the deadliest infectious disease globally.

 

Read also:

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Overcoming difficulties developing an HIV vaccine http://www.eatg.org/news/overcoming-difficulties-developing-an-hiv-vaccine/ Wed, 10 Jan 2018 22:50:21 +0000 http://www.eatg.org/?post_type=news&p=7171 The development of a vaccine that protects against HIV infections has proven extraordinarily difficult. One of the reasons is that naïve precursor B cells that can give rise to mature B cells producing broadly neutralizing antibodies — a requirement for a successful antibody-based HIV vaccine — are considered to be exceedingly rare within the average human.

Publishing in the December 26, 2017, online issue of the journal Immunity, researchers at the La Jolla Institute for Allergy and Immunology (LJI) now show that despite their low frequency these B cell precursors can be successfully primed to prevail over their B cell competitors under the right conditions.

“We had shown in an earlier study that we can find these B cells in most humans but at a very low cell frequency, about one in a million. What we didn’t know was whether that was enough cells to elicit an effective immune response,” says senior author Shane Crotty, Ph.D., a professor in LJI’s Division of Vaccine Discovery. “We had the numbers, but we didn’t know what they actually meant.” By providing an answer, the current study closes the knowledge gap about competition between different immune responses and establishes defined benchmarks vaccine candidates should be compared against for consideration before they are put into clinical trials.

“As the vaccine field is getting much more sophisticated we need to understand the requirements for good vaccine design so we can elicit the immune response we want as opposed to a competing one,” explains postdoctoral researcher and first author Robert Abbott, Ph.D. “What we found is that when you reduce the precursor frequency to one in a million, the vaccine candidate’s affinity becomes a distinct separating factor for competitive success of a B cell.”

Germinal centers, specialized areas within lymph nodes, are the central arena where the competition for immunodominance plays out. Before B cells are able to produce neutralizing antibodies they have to persevere in a competitive, multi-step maturation process that selectively promotes the proliferation of B cells that produce antibodies that bind the best to the virus or other immune stimulant. B cells undergo a specialized process called affinity maturation in which they undergo successive rounds of mutation and selection ultimately resulting in increasingly better antiviral antibodies.

“B cells have to actually transform their normal DNA, in some instances quite substantially, to be able to effectively chase the virus over time” says Abbott. In the B cells that produce broadly neutralizing anti-HIV antibodies, meaning those that can bind to the many variants that occur rapidly in different individuals as the virus tries to evade the immune response, the level of mutation can be extraordinarily high, changing 30 to 50 % of the genes encoding them. It helps explain why it can take years before HIV-infected individuals start making these neutralizing antibodies. But it also presents a unique challenge for an HIV vaccine since conventional vaccination protocols are unlikely to generate enough of the desired mutations to enable protective antiviral immune response.

That led Scripps Research Institute professor and co-author William Schief, Ph.D., to conceive a sophisticated, multi-step protocol designed to shepherd B cells closer and closer toward producing broadly neutralizing antibody. The process is based on vaccinating with a series of gradually changing immunogens, which are the substances related to the virus used to elicit the immune response. The process is comparable to teaching a B cell that recognizes squares to bind to circles by using pentagons as an intermediate step.

The vaccination step studied by LJI researchers was the first or ‘priming’ step, which is designed to expand the pool of suitable precursor B cells. To assess the roles of immunogen affinity and precursor frequency during that first step, the team developed a mouse model that allowed them to recapitulate physiological human B cell frequencies. They were particularly interested in B cells that give rise to ‘VRC01-class’ antibodies, which are some of the best broadly neutralizing antibodies found in HIV-infected individuals.

“The idea here is to find shortcuts that focus on B cells that look the right way and teach them to go into the right direction,” says Crotty. “After this step, immunized people won’t have neutralizing antibodies but the idea is you get more of the B cells that could — after some other help and with additional immunizations — develop into B cells that produce neutralizing antibodies.” It is a general vaccine strategy that has never been tested before in humans but given the right immunogen it can work, predicts Crotty.

The work was funded in part by NIAID grants CHAVI-ID UM1 AI100663, R01 AI073148, R01 AI12883, LJI T32 AI125179, the international AIDS Vaccine Initiative (IAVI) with support from United States Agency for International Development, the Ministry of Foreign Affairs of the Netherlands and the Bill & Melinda Gates Foundation.

Journal Reference:

  1. Robert K. Abbott, Jeong Hyun Lee, Sergey Menis, Patrick Skog, Meghan Rossi, Takayuki Ota, Daniel W. Kulp, Deepika Bhullar, Oleksandr Kalyuzhniy, Colin Havenar-Daughton, William R. Schief, David Nemazee, Shane Crotty. Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens. Immunity, 2017; DOI: 10.1016/j.immuni.2017.11.023
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Gene therapy using CAR T-cells could provide long-term protection against HIV http://www.eatg.org/news/gene-therapy-using-car-t-cells-could-provide-long-term-protection-against-hiv/ Wed, 10 Jan 2018 22:48:43 +0000 http://www.eatg.org/?post_type=news&p=7170 FINDINGS

Through gene therapy, researchers engineered blood-forming stem cells (hematopoietic stem/progenitor cells, or HSPCs) to carry chimeric antigen receptor (CAR) genes to make cells that can detect and destroy HIV-infected cells. These engineered cells not only destroyed the infected cells, they persisted for more than two years, suggesting the potential to create long-term immunity from the virus that causes AIDS.

BACKGROUND

Antiviral drugs can suppress the amount of HIV in the body to nearly undetectable levels, but only an effective immune response can eradicate the virus. Researchers have been seeking a way to improve the body’s ability to combat the virus by engineering blood-forming stem cells to specifically target and kill HIV-infected cells for the life of the individual. Although chimeric antigen receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer – and show promise in treating HIV-1 infection – the therapy may not impart long-lasting immunity. Researchers, physicians and patients need T cell-based products that can respond to malignant or infected cells that may reappear months or years after treatment.

METHOD

Because HIV uses CD4 to infect cells, the researchers used a CAR molecule that hijacks the essential interaction between HIV and the cell surface molecule CD4 to make stem cell-derived T-cells target infected cells. When the CD4 on the CAR molecule binds to HIV, other regions of the CAR molecule signal the cell to become activated and kill the HIV infected cell. The researchers found that, in test animals, modification of the blood-forming stem cells resulted in more than two years of stable production of CAR-expressing cells without any adverse effects. In addition, these cells were widely distributed throughout the lymphoid tissues and gastrointestinal tract, which are major anatomic sites for HIV replication and persistence in infected people. Most important, engineered CAR T-cells showed efficacy in attacking and killing HIV-infected cells.

IMPACT

These findings are the first to show that blood-forming stem cells can be modified with a CAR therapy that can safely engraft in the bone marrow, mature and become functional immune cells throughout the body. This could lead to the development of an approach allowing for safe, lifelong immunity to HIV. Such an approach is likely to work best when performed in combination with other treatment strategies, such as antiretroviral therapy. Researchers hope that this type of therapy could reduce infected individuals’ dependence on antiviral medications, lower the cost of therapy, and permit the possible eradication of HIV from its hiding places in the body. The approach also has potential against other infections or malignancies.

###

Journal Reference:

  1. Anjie Zhen, Christopher W. Peterson, Mayra A. Carrillo, Sowmya Somashekar Reddy, Cindy S. Youn, Brianna B. Lam, Nelson Y. Chang, Heather A. Martin, Jonathan W. Rick, Jennifer Kim, Nick C. Neel, Valerie K. Rezek, Masakazu Kamata, Irvin S. Y. Chen, Jerome A. Zack, Hans-Peter Kiem, Scott G. Kitchen. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS. PLOS Pathogens, 2017; DOI: 10.1371/journal.ppat.1006753
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STIs in the era of antiretroviral-based HIV prevention http://www.eatg.org/news/stis-in-the-era-of-antiretroviral-based-hiv-prevention/ Wed, 10 Jan 2018 22:46:26 +0000 http://www.eatg.org/?post_type=news&p=7172 Priorities for discovery research, implementation science, and community involvement

Summary points

  • Persons living with HIV who achieve sustained viral suppression with antiretroviral therapy can avoid sexual transmission of HIV without using condoms.
  • Similarly, pre-exposure prophylaxis with tenofovir-emtricitabine in HIV-uninfected persons is highly effective.
  • With this background, rates of sexually transmitted infections are increasing in some HIV-infected populations, and in some at risk for HIV acquisition.
  • The implications require reassessment of the alignment and prioritization of HIV research funding, public health policy, and community engagement.

 

To read the full publication in PLOS Medicine, click here.

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Post-exposure prophylaxis helps prevent chlamydia, syphilis in high-risk MSM http://www.eatg.org/news/post-exposure-prophylaxis-helps-prevent-chlamydia-syphilis-in-high-risk-msm/ Wed, 10 Jan 2018 21:51:56 +0000 http://www.eatg.org/?post_type=news&p=7169 Post-exposure prophylaxis (PEP) with doxycycline can sharply reduce the risk of chlamydia and syphilis in high-risk men who have sex with men (MSM), according to a substudy of the ANRS IPERGAY trial.

“This is a first finding that’s interesting because of the dramatic decline in incidence, but it has to be confirmed, and especially what has to be confirmed is the lack of impact on the selection of antibiotic resistance in chlamydia and syphilis,” Dr. Jean-Michel Molina of the Hopital Saint-Louis in Paris, who directed the trial, told Reuters Health in a telephone interview.

In the ANRS IPERGAY trial (http://bit.ly/1Tit0xp), on-demand pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate plus emtricitabine dramatically reduced HIV infections in high-risk MSM who did not use condoms. The new study, an open-label extension of that trial, included 232 men on PrEP randomly assigned to take one dose of 200 mg doxycycline within 24 hours after having sex (PEP), or to receive no PEP (control). Study participants were tested for STIs every two months.

During a median follow-up of 8.7 months, a new STI was diagnosed in 73 participants: 29 PEP patients and 45 controls (9-month probability of a new STI 22% and 42%, respectively; hazard ratio, 0.53; P=0.008).

Participants in the PEP group took a median of 680 mg of doxycycline, or fewer than seven pills, per month.

The risk of serious adverse events was similar with or without PEP, although the likelihood of gastrointestinal adverse events was higher with PEP (53% vs. 41% without PEP).

Although PEP was associated with significantly lower risks of first chlamydia or first syphilis infection, it did not reduce gonorrhea risk. This finding was expected, Dr. Molina noted, as gonorrhea is already resistant to doxycycline – and not amenable to PEP because it can quickly develop resistance to antibiotics.

Of the study participants diagnosed with STIs, 71% had no symptoms. Regularly testing at-risk people for STIs and treating them – and their partners – early can help reduce the spread of these diseases, just as this approach helped address the HIV epidemic, Dr. Molina said. “We have to change the way we deal with STIs, because it would not be acceptable to test for HIV only people with AIDS,” he added. “It makes sense why you cannot break the cycle of the increased rate of STIs if you test and treat people only when they are symptomatic. You need to act much earlier and test more frequently earlier in people who are at risk.”

At present the Centers for Disease Control and Prevention recommends STI testing every three months, Dr. Molina noted, but only for MSM. “Doctors should be taught that everyone should be tested for STIs, like we ask people to be tested for HIV,” he said. “Anyone who has different sex partners should be tested, and not waiting for symptoms to develop.”

He and his colleagues plan to confirm their findings in a larger population – and to continue to watch for antibiotic resistance.

In an accompanying editorial, Dr. Christopher K. Fairley of Alfred Health and Dr. Eric P.F. Chow of Monash University, both in Melbourne, Victoria, Australia, write: “Given the absence of data on population-wide benefits and antibiotic resistance, we agree with Molina and colleagues that any recommendation in favour of doxycycline prophylaxis is premature. The absence of a recommendation, however, will not prevent clinicians from prescribing doxycycline in individual circumstances, but we should use this use of doxycycline as an opportunity to accurately define the risks and benefits of doxycycline prophylaxis in this setting.”

ANRS (France Recherche Nord & Sud Sida-HIV Hepatites) and the Bill & Melinda Gates Foundation funded the study.

By Anne Harding

SOURCES: http://bit.ly/2Ccupn8 and http://bit.ly/2BtX3Ac

Lancet Infect Dis 2017.

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Prolonged prophylaxis prevents HIV transmission during breastfeeding http://www.eatg.org/news/prolonged-prophylaxis-prevents-hiv-transmission-during-breastfeeding/ Wed, 10 Jan 2018 21:47:19 +0000 http://www.eatg.org/?post_type=news&p=7168 Both maternal antiretroviral therapy (mART) and prolonged infant nevirapine prophylaxis (iNVP) safely help to prevent breastfeeding mothers from passing HIV-1 to their infants, according to long-term data from the PROMISE trial.

Both mART and iNVP are safe and effective for preventing transmission of the virus from mother to baby during breastfeeding, but past research has looked only at interventions lasting up to 12 months, Dr. Patricia Flynn of St. Jude Children’s Research Hospital in Memphis and her colleagues note in their December 11 report in the Journal of Acquired Immune Deficiency Syndromes.

“Because increased morbidity and mortality have been associated with weaning compared to continued breastfeeding through the second year of life in HIV-1 exposed infants, breastfeeding beyond 12 months, and interventions to reduce HIV-1 transmission during breastfeeding will be required to maximize infant HIV-1 free survival,” they add.

The PROMISE (Promoting Maternal Infant Survival Everywhere) trial included 2,431 breastfeeding, HIV-infected mothers with high CD4 counts (at least 350 cells/mm3) and their HIV-negative infants from 14 sites in sub-Saharan Africa and India. Mother-child pairs were enrolled six to 14 days postpartum and randomly assigned to receive mART or iNVP. Treatment continued for up to 18 months after delivery.

Seven infants in each study arm became infected with HIV (<0.6% in both groups). HIV-free survival at 24 months was 97.1% with mART and 97.7% with iNVP.

Median time to breastfeeding cessation was 16 months in both groups, and they had similar incidences of life-threatening and fatal adverse events. Fewer than 1% of women and 2% of babies stopped treatment because of toxicity.

World Health Organization guidelines recommend that everyone with HIV be on ART for life, Dr. Flynn and her team note. “Despite these recommendations, due to postpartum adherence problems, many women experience rebound viremia, resulting in continued postnatal transmission,” they add. The findings show that iNVP can be a safe, effective option when adherence to ART is difficult, they conclude.

Dr. Flynn was not available for an interview by press time.

SOURCE: http://bit.ly/2p25rUM

J Acquir Immune Defic Syndr 2017.

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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-35/ Wed, 10 Jan 2018 21:39:31 +0000 http://www.eatg.org/?post_type=news&p=7165

Aidspan: Global Fund Observer

Aidspan, an independent watchdog of the Global Fund to Fight AIDS, Tuberculosis and Malaria, published Issue 328 of the “Global Fund Observer.” The newsletter includes articles on various topics, including Nigeria’s malaria, TB, and HIV funding; the Global Fund Board’s approval of an additional $1.38 billion in grants for 2017-2019; and Zambia’s request for TB/HIV funding.

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The first generation to grow old with HIV are ageing faster http://www.eatg.org/news/the-first-generation-to-grow-old-with-hiv-are-ageing-faster/ Tue, 09 Jan 2018 22:59:27 +0000 http://www.eatg.org/?post_type=news&p=7160 David Crawford is among the first generation getting old with HIV.

When Mr Crawford was diagnosed with the virus in 1984, the then 29-year-old thought he’d been given a death sentence.

Thirty-three years later, it’s more of a chronic disease thanks to the emergence of potent combination antiretrovirals introduced in the mid-90s.

But no one, not Mr Crawford, his peers, the doctors or HIV researchers anticipated the monumental health complications this ageing population would be forced to grapple with.

“We’re sailing into unknown horizons,” said the registered nurse and treatment officer who runs the Genesis support program at Positive Life NSW in Surry Hills for people living with HIV.

By 2020, more than 40 per cent of people living with HIV will be over 60, ageing in a health system that has not planned for the significant burden of their complex physical and mental health needs.

The virus combined with the often deleterious concoctions of early drug treatments has accelerated their ageing process and immune system decay, potentially by more than a decade.

“We’re caught in no-man’s land. We were on the edge of death and we were pulled back with these toxic meds, but the damage was done,” Mr Crawford said.

People ageing with HIV are getting older faster, said Lucette Cysique, lead researcher of the NeuroHIV group at Neuroscience research Australia (NeuRA) and UNSW.

“We’re seeing people in their 60s with presentations [of chronic diseases] we would usually see in people 70-plus,” she said, including cognitive decline, vascular and metabolic diseases.

They are the “D-drug” generation, Mr Crawford said, a reference to the toxic drugs with D-heavy acronyms (DDI, DDC, D4T) used before the introduction of combination antiretrovirals that irreparably damaged patients’ metabolic, nervous and neurological systems.

“They’ve got AIDS-related cancers, blindness, high incidences of cardiovascular disease, musculoskeletal problems, and there are a lot of mental health issues.”

The case that most shocked him was a man he meet at a World AIDS Day event on December 1.

A particularly toxic medication the man had been prescribed in the early 90s had stripped his face and limbs of fat and left him with a distended stomach.

“His legs were like sticks and face was so badly damaged it was skin and bone … he told my partner and I that he couldn’t find anyone to go out with him.

“He has to deal with the stigma of HIV, the [psychological] pain that goes with it on top of the side effects caused by the drugs,” he said.

There are growing concerns that this ageing HIV population are at greater risk of a double-barrel effect of cognitive decline and mental health problems, yet little is known how they will present in their elderly years.

Mounting evidence suggests HIV accelerates age-associated cognitive decline with alarming prevalence.

Up to 50 per cent of bisexual and gay men with HIV who are on treatment experience some form of mild neurocognitive dysfunction by their mid-50s, Dr Cysique said.

Up to 30 per cent will develop more serious neurocognitive problems and 2 to 4 per cent will develop early onset dementia.

“We’re wondering what the hell is this going to look like in 10 years?” Dr Cysique said.

“Is mild cognitive dysfunction predictive of dementia later in life [among people with HIV]? We don’t know and we need to find out.”

When Mr Crawford came off his antiretrovirals as part of a trial in 2008, his cognitive function deteriorated to 45 per cent capacity within five years.

“Couldn’t remember four-digit pin, couldn’t remember my own name.

“I had massive headaches, I was incredibly suicidal, I slept for incredibly long periods. I was really sick and came within about six months of doing permanent damage before I went back on the antiretrovirals,” he said.

Social isolation – common among people living with HIV – was a major risk factor for mental illness.

The lifetime prevalence of anxiety and depression symptoms was 40 per cent among bisexual and gay men with HIV, Dr Cysique said.

One-third of people with the virus will develop a stress disorder and bisexual and gay men with HIV have 2½ times the rate of hospitalisation due to mental health and HIV-related neurological complications.

More than one in four have contemplated suicide and 13 per cent have attempted suicide, Dr Cysique said, yet mental health care in Australia was not geared towards the elderly with HIV.

The sudden closure in November of H2M at St Vincent’s Hospital, the only dedicated mental health service in Sydney, was “a catastrophe”, she said.

“There needs to be more than generic health services, and support for community [peer-run support] programs where people getting older with HIV can come together, stay positive and not socially isolate,” she said.

Her search group is bringing together a multidisciplinary team of psychiatrists, psychologists, neuropsychologists, neurologists, neuroscientists and social scientists in Australia and internationally to pool research into HIV and ageing and mental health.

The project aims to guide best clinical practices for treatments and interventions to help support people with HIV to support healthy ageing in people living withHIV.

“The reason I come to work every day is to keep supporting the community and legacy to my friends who didn’t make it,” Mr Crawford said.

“They get me out of bed every day. I’m fortunate to have made it.”

By Kate Aubusson

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Common birth control shot linked to risk of HIV infection http://www.eatg.org/news/common-birth-control-shot-linked-to-risk-of-hiv-infection/ Tue, 09 Jan 2018 22:55:53 +0000 http://www.eatg.org/?post_type=news&p=7161 Replacing the popular contraceptive shot known as DMPA with alternative methods of contraception could help protect women in sub-Saharan Africa and other high-risk regions from becoming infected with HIV, according to a comprehensive review of available evidence published in the journal Endocrine Reviews.

“Human studies suggest DMPA use may raise the risk of HIV infection in exposed women by about 40 percent,” said Zdenek Hel, Ph.D., professor in the University of Alabama at Birmingham Department of Pathology, UAB School of Medicine, and a co-author of the study.“Importantly, we know that some other forms of contraceptive methods do not show the same deleterious effect on the immune function in cell culture, small animals or human studies.

As of 2016, 36.7 million people worldwide were living with HIV, according to UNAIDS, the Joint United Nations Program on HIV/AIDS. More than half of those people live in eastern or southern Africa. AIDS is the most advanced stage of the HIV viral infection.

DMPA — or depot-medroxyprogesterone acetate — is the predominant contraceptive in sub-Saharan Africa, administered as a birth control shot every three months. It is estimated to be used by more than 50 million women worldwide. “It is also used at a relatively high frequency in Alabama and other Southern states in the United States,” Hel said.

In the research review, first author Janet P. Hapgood, Ph.D., University of Cape Town, South Africa; Hel; and Charu Kaushic, McMaster University, Hamilton, Ontario, Canada, examined the underlying biological mechanisms that could contribute to increased risk of HIV infection for certain hormonal contraceptives but not others.

“To protect individual and public health, it is important to ensure women in areas with high rates of HIV infection have access to affordable contraceptive options,” Hapgood said. “Increasing availability of contraceptives that use a form of the female hormone progestin different from the one found in DMPA could help reduce the risk of HIV transmission.”

In addition to these clinical studies, the authors examined animal, cell and biochemical research on the form of progestin used in DMPA — medroxyprogesterone acetate, or MPA. The analysis revealed MPA acts differently from other forms of progestin used in contraceptives. In the cells of the genital tract that can come in contact with HIV, MPA behaves like the stress hormone cortisol.

“The increased rate of HIV infection among women using DMPA contraceptive shots is likely due to multiple reasons, including decreases in immune function and the protective barrier function of the female genital tract,” Hapgood said. “Studying the biology of MPA helps us understand what may be driving the increased rate of HIV infection seen in human research. These findings suggest other forms of birth control should rapidly replace DMPA shots.”

“Access to safe, effective and affordable contraception is critical for women’s health worldwide,” Hel said. “Up to 50 percent of unintended pregnancies in Africa end in abortion, often performed in an unsafe manner. We have to do everything in our power to rapidly replace DMPA with a safer alternative. The word ‘replace’ is critical; DMPA cannot just be taken off the shelves as many women would be left with no available option. Ideally, women should have access to a full range of contraceptive choices and should be informed regarding the benefits and potential dangers associated with each option.”

The study, “Hormonal Contraception and HIV-1 Acquisition: Biological Mechanism,” was supported by the National Institutes of Health and the Canadian Institutes of Health Research. Endocrine Reviews is a publication of the Endocrine Society, the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

To offset the immunosuppressive effect of DMPA, a new formulation called Sayana Press has recently been developed that administers 31 percent less hormone via a subcutaneous administration. In a manuscript released this week, Chelsea Polis, Ph.D., Guttmacher Institute, and Sharon Achilles, M.D., Ph.D., University of Pittsburgh, together with Hapgood and Hel, address the potential effect of reducing the dose of DMPA. The authors conclude that, while the lower dose is likely to result in a partial reduction of the systemic concentration of the hormone shortly after delivery, it is not likely to ameliorate the overall negative impact of MPA on biological responses.

“Unfortunately, simply reducing the dose of DMPA is not a solution,” Hel said. “We need a qualitatively new approach. However, I am an optimist. I believe a solution is already in our hands. The real effort now lies in the implementation of the knowledge accumulated over the last six years into clinical practice and public health policy.”

The study, titled “Is a lower-dose, subcutaneous contraceptive injectable containing depotmedroxyprogesterone acetate likely to impact women’s risk of HIV?” was published by the journal Contraception and was supported by the National Institutes of Health and the Guttmacher Institute.

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Merck submits New Drug Applications for doravirine to FDA http://www.eatg.org/news/merck-submits-new-drug-applications-for-doravirine-to-fda/ Tue, 09 Jan 2018 22:54:45 +0000 http://www.eatg.org/?post_type=news&p=7156 FDA accepts New Drug Applications for Merck’s doravirine, the company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), for treatment of HIV-1 infection

KENILWORTH, N.J., January 8, 2018 – Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review two New Drug Applications (NDAs) for doravirine, the company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection in adults. The NDAs include data for doravirine (DOR) as a once-daily tablet for use in combination with other antiretroviral agents, and for use of doravirine with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) in a once-daily fixed-dose combination single tablet as a complete regimen (DOR/3TC/TDF). The FDA has set a target action date of Oct. 23, 2018, for both applications under the Prescription Drug User Fee Act (PDUFA).

“Since the earliest days of the epidemic, Merck has sustained our commitment to research and meeting the needs of people living with HIV. Doravirine was engineered by our research team to provide a meaningful new treatment approach and address unmet medical needs in the treatment of HIV-1 infection,” said Dr. George Hanna, associate vice president, global clinical development, Merck Research Laboratories. “We have been pleased with the clinical findings to date and look forward to working with the FDA as it reviews our applications.”

The NDAs are based upon the findings at Week 48 of two ongoing Phase 3 trials, DRIVE-FORWARD and DRIVE-AHEAD, evaluating the efficacy and safety of doravirine and the fixed-dose combination regimen of DOR/3TC/TDF, respectively. These data were previously presented at CROI-2017 and IAS 2017, respectively.

About Doravirine

Doravirine (MK-1439, DOR) is an investigational NNRTI being evaluated by Merck for the treatment of HIV-1 infection. DOR is being evaluated in several ongoing clinical trials both as a once-daily single-entity tablet in combination with other antiretroviral agents in a tailored regimen, and as a once-daily fixed-dose combination (DOR/3TC/TDF) in a complete single tablet regimen. Phase 3 trials include DRIVE-FORWARD, a trial comparing DOR to once-daily ritonavir-boosted darunavir (DRV+r), each administered in combination with FTC/TDF or abacavir (ABC)/3TC, in treatment-naïve adults; DRIVE-AHEAD, a trial comparing DOR/3TC/TDF to EFV/FTC/TDF in treatment-naïve adults; and DRIVE-SHIFT, a trial evaluating a switch to DOR/3TC/TDF in HIV-1 infected adults who are currently virologically suppressed on another antiretroviral regimen. Other ongoing Phase 2 clinical trials include an evaluation of DOR/3TC/TDF in treatment-naïve adults with transmitted resistance to NNRTIs and in individuals switching from EFV due to intolerability.

About DRIVE-FORWARD

DRIVE-FORWARD is a multicenter, double-blind, randomized non-inferiority trial in which 769 treatment-naïve adults with HIV-1 infection received either DOR (100 mg) or DRV+r (800 mg +100 mg), both administered orally once-daily in combination with either TDF/FTC or ABC/3TC. The primary endpoint of the clinical trial was the proportion of participants with HIV-1 RNA less than 50 copies/mL at Week 48. Secondary endpoints included an evaluation of the effects of DOR and DRV+r on fasting serum lipids, change from baseline in CD4+ T-cell count, and evaluation of safety and tolerability. The trial consists of a 96-week double-blind treatment period (base study) and an open label extension after participants complete the base study. For further information regarding DRIVE-FORWARD please visit www.clinicaltrials.gov clinical trial registry number NCT02275780.

About DRIVE-AHEAD

DRIVE-AHEAD is an ongoing Phase 3 multicenter, double-blind, randomized, active comparator-controlled clinical trial evaluating the safety and efficacy of a once-daily, single-tablet, fixed-dose combination consisting of DOR/3TC/TDF (100mg/300mg/300mg) versus a once daily, single-tablet, fixed-dose combination of EFV/FTC/TDF (600mg/200mg/300mg) in treatment-naïve HIV-1 infected adults. The primary endpoint of the clinical trial was the proportion of participants with HIV-1 RNA less than 50 copies/mL at Week 48. The primary safety endpoint was the proportion of participants with neuropsychiatric adverse events through Week 48 in the following pre-specified categories: dizziness, sleep disorders and disturbances, and the inability to think clearly or concentrate. Secondary endpoints included an evaluation of the effects of DOR/3TC/TDF and EFV/FTC/TDF on fasting serum lipids, change from baseline in CD4+ T-cell count, and evaluation of safety and tolerability. The trial consists of a 96-week double-blind treatment period (base study) and an open label extension after participants complete the base study. For further information regarding DRIVE-AHEAD please visit www.clinicaltrials.gov clinical trial registry number NCT02403674.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn. For more information, visit www.merck.com and connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2016 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

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Suboptimal ART adherence associated with greater inflammation in patients with HIV http://www.eatg.org/news/suboptimal-art-adherence-associated-with-greater-inflammation-in-patients-with-hiv/ Tue, 09 Jan 2018 22:53:41 +0000 http://www.eatg.org/?post_type=news&p=7158 Recently published findings indicate that suboptimal adherence to ART is associated with activation of coagulation and enhanced residual inflammation among patients with HIV, even if patients have already achieved virologic suppression.

“Recently, suboptimal ART adherence has emerged as a potential contributor to residual inflammation in [people living with HIV], even if it is sufficient to achieve and sustain plasma viral suppression through conventional assays,” Jose R. Castillo-Mancilla, MD, associate professor of medicine at the University of Colorado Anschutz Medical Campus, and colleagues wrote. “These observations have emphasized the potential biological differences that could exist between complete and suboptimal ART adherence in order to maximize the therapeutic benefit of ART. Whether these associations can also be identified in a large, multinational diverse population remains unknown.”

The researchers performed a retrospective analysis evaluating the relationship of adherence to ART with inflammation and coagulation activation among patients enrolled in the Strategies for Management of ART (SMART) study, a multinational, randomized clinical trial of 5,472 patients with HIV aged 13 years and older. All patients were receiving ART, had completed a questionnaire about adherence and had available measurements of viral load. The analysis focused on patients who had viral loads of less than 200 copies/mL and it was limited to the baseline clinic visit.

Overall, 3,963 patients had a completed adherence questionnaire and available viral load measurement and were taking ART. More than three quarters (77%) were suppressed to less than 200 copies/mL.

Patients who reported suboptimal adherence had 9% higher plasma concentrations of interleukin 6 compared with those who reported 100% adherence (95% CI; 1%-18%), the researchers reported. Similarly, those with suboptimal ART adherence demonstrated 11% higher concentrations of D-dimer (95% CI; 1%-22%).

“We demonstrated that suboptimal ART adherence, even if it results in virologic suppression by conventional clinical assays, is associated with enhanced residual inflammation and activation of coagulation in [people living with HIV] on chronic ART,” the researchers wrote. “These findings replicate previous cohort observations and highlight the importance of optimal and durable ART adherence as a potential factor to improve morbidity and mortality in HIV disease.”

Castillo-Mancilla JR, et al. Open Forum Infect Dis. 2017;doi:10.1093/ofid/ofx275.

By Andy Polhamus

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Immediate HIV treatment has little impact on risk of future drug resistance http://www.eatg.org/news/immediate-hiv-treatment-has-little-impact-on-risk-of-future-drug-resistance/ Tue, 09 Jan 2018 22:48:54 +0000 http://www.eatg.org/?post_type=news&p=7157 Starting antiretroviral therapy (ART) immediately rather waiting until a person’s CD4 count falls below 500 cells/µL has almost no impact on the person’s risk of developing antiretroviral resistance over the next seven years, according to a study published online in the journal AIDS. In this 51,000-person analysis, the impact of immediate ART on acquired drug resistance disappeared almost completely among people starting treatment in 2005 or later.

Antiretroviral guidelines in the U.S. and throughout the world recommend ART immediately after HIV diagnosis, regardless of CD4 count. Research ties immediate ART to a lower risk of developing serious HIV-related and non-HIV-related conditions, as well as to lower HIV transmission risk. But concern persists that a longer overall duration of treatment resulting from immediate ART boosts a person’s chances of developing acquired antiretroviral resistance. To address this concern, researchers with the HIV-CAUSAL Collaboration in Europe and the U.S. conducted this prospective analysis.

The study focused on routinely collected resistance data from six cohorts — one each in Greece, the Netherlands, Spain, and Switzerland, as well as two in the United Kingdom. Resistance study participants were at least 18 years old and had their viral load and CD4 count measured within three months of each other before they started ART. (No participants had an AIDS-defining condition.)

The HIV-CAUSAL team compared emergence of resistant virus in three ART-initiation groups: (1) immediate ART (started within three months of baseline), (2) ART initiated within three months of reaching a CD4 count below 500 cells/µL, and (3) ART initiated within three months of reaching a CD4 count below 350 cells/µL or receiving an AIDS diagnosis.

The primary outcome was acquired resistance to an antiretroviral up to seven years after follow-up began, using the Stanford University resistance database to assess resistance levels. To compare resistance rates with the three treatment strategies, the researchers used a regression model, the parametric g-formula, adjusted for fixed baseline variables and for time-varying confounders (CD4 count, viral load, AIDS, resistance testing, and nonnucleoside antiretroviral class versus other classes).

Among the 50,981 eligible participants, 80% were men. The median baseline age was 35 years, and the median baseline CD4 count was 405 cells/µL. Almost three-quarters of participants, 71%, started follow-up after 2004. Of the 31,969 people (63%) who started ART, 3,207 (10%) did so with a CD4 count above 500 cells/µL. Among 22,161 participants (43%) tested for transmitted HIV drug resistance before starting ART and within 12 months of baseline, 6.1% had detectable resistant virus.

Overall risk of acquired resistance seven years after baseline was 2.7%. Seven-year estimated resistance risk did not differ significantly among any of the three ART groups: immediate ART (3.2%, 95% confidence interval [CI] 2.8 to 3.5), ART initiation below 500 cells/µL (3.1%, 95% CI 2.7% to 3.3%), and ART initiation below 350 cells/µL (2.8%, 95% CI 2.5% to 3.1%).

When the analysis was restricted to people with a baseline date between 2005 and 2015, estimated seven-year risk of acquired resistance varied hardly at all among the three groups: immediate ART (1.9%, 95% CI 1.8 to 2.5), initiation below 500 cells/µL (1.9%, 95% CI 1.7 to 2.4), and initiation below 350 cells/µL (1.8%, 95% CI 1.7 to 2.2). Seven-year acquired resistance estimates also virtually overlapped with an analysis restricted to people with a baseline CD4 count above 500 cells/µL: immediate ART (1.6%, 95% CI 1.2 to 2.3), initiation below 500 cells/µL (1.9%, 95% CI 1.4 to 2.4), and initiation below 350 cells/µL (1.6%, 95% CI 1.2 to 2.1). Results did not change substantially when researchers sequentially excluded each of the six cohorts from the analysis.

The investigators believe their findings indicate “it is unlikely that the clinical benefits of early ART initiation demonstrated by randomized trials and observational studies will be lessened by development of acquired drug resistance.” They note that starting ART immediately raised seven-year acquired resistance risk only 0.13% compared with starting ART at a CD4 count below 500 cells/µL, and by only 0.37% compared with starting ART below 350 cells/µL.

These minimal differences may be even smaller today, the authors add, because their study sample underrepresented treatment with newer protease inhibitors and integrase inhibitors associated with low resistance rates.

By Mark Mascolini

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New long-acting, less-toxic HIV drug suppresses virus in humanized mice http://www.eatg.org/news/new-long-acting-less-toxic-hiv-drug-suppresses-virus-in-humanized-mice/ Tue, 09 Jan 2018 22:32:26 +0000 http://www.eatg.org/?post_type=news&p=7155 A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate to enhance current HIV treatment regimens — without increasing toxic side effects, the researchers said.

The finding builds on the work of senior co-authors Karen S. Anderson and William L. Jorgensen, who used computational and structure-based design methods to develop a class of compounds, that target a viral protein essential for HIV to replicate. The researchers refined this class of compounds to boost potency, lower toxicity, and improve drug-like properties in order to identify a promising preclinical drug candidate. In collaboration with Priti Kumar’s lab at Yale, the drug candidate was tested in mice with transplanted human blood cells and infected with HIV.

In the humanized mice, the compound achieved key goals of HIV treatment: It suppressed the virus to undetectable levels in the blood; it protected the immune cells that the virus infects; and it worked synergistically with approved HIV medications, the researchers said.

Additionally, working with Yale drug delivery expert Mark Saltzman and his laboratory, the researchers found that the effects of a single dose of the compound — delivered in a long-acting nanoparticle form — lasted for nearly a month.

While further testing is needed, the compound has potential for improving treatment for HIV, which affects 37 million people worldwide, said Anderson. “Our drug candidate works synergistically with all current classes of HIV drugs, as well as some that are also being tested in clinical trials. It enhances their potency and could be a better combination medication.”

Other Yale authors are Shalley N. Kudalkar, Jagadish Beloor, Elias Quijano, Krasimir A. Spasov, Won-Gil Lee, and José A. Cisneros.

The study, published by Proceedings of the National Academy of Sciences (PNAS), was supported by National Institute of Health grants.

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Usage remains low for pill that can prevent HIV infection http://www.eatg.org/news/usage-remains-low-for-pill-that-can-prevent-hiv-infection/ Tue, 09 Jan 2018 22:20:03 +0000 http://www.eatg.org/?post_type=news&p=7154 From gritty neighborhoods in New York and Los Angeles to clinics in Kenya and Brazil, health workers are trying to popularize a pill that has proven highly effective in preventing HIV but which — in their view — remains woefully underused.

Marketed in the United States as Truvada, and sometimes available abroad in generic versions, the pill has been shown to reduce the risk of getting HIV from sex by more than 90 percent if taken daily. Yet worldwide, only about a dozen countries have aggressive, government-backed programs to promote the pill. In the U.S., there are problems related to Truvada’s high cost, lingering skepticism among some doctors and low usage rates among black gays and bisexuals who have the highest rates of HIV infection.

“Truvada works,” said James Krellenstein, a New York-based activist. “We have to start thinking of it not as a luxury but as an essential public health component of this nation’s response to HIV.”

A few large U.S. cities are promoting Truvada, often with sexually charged ads. In New York, “Bare It All” was among the slogans urging gay men to consult their doctors. The Los Angeles LGBT Center — using what it called “raw, real language” — launched a campaign to increase use among young Latino and black gay men and transgender women.

“We’ve got the tools to not only end the fear of HIV, but to end it as an epidemic,” said the center’s chief of staff, Darrel Cummings. “Those at risk have to know about the tools, though, and they need honest information about them.”

In New York, roughly 30 percent of gay and bisexual men are using Truvada now, up dramatically from a few years ago, according to Dr. Demetre Daskalakis, a deputy commissioner of the city’s health department.

However, Daskalakis said use among young black and Hispanic men — who account for a majority of new HIV diagnoses — lags behind. To address that, the city is making Truvada readily available in some clinics in or near heavily black and Hispanic neighborhoods.

“We like to go to the root of the problem,” said Daskalakis, who personally posed for the “Bare It All” campaign.

According to the U.S. Centers for Disease Control and Prevention , Truvada would be appropriate for about 1.2 million people in the U.S. — including sex workers and roughly 25 percent of gay men. Gilead Scientific, Truvada’s California-based manufacturer, says there are only about 145,000 active prescriptions for HIV prevention use.

Under federal guidelines, prime candidates for preventive use of Truvada include some gay and bisexual men with multiple sexual partners, and anyone who does not have HIV but has an ongoing sexual relationship with someone who has the virus.

Abroad, a few government health agencies — including those in France, Norway, Belgium, Kenya, South Africa, Brazil and some Canadian provinces— have launched major efforts to promote preventive use of Truvada or generic alternatives, providing it for free or a nominal charge. In Britain, health officials in Scotland and England recently took steps to provide the medication directly through government-funded programs, though in England it’s in the form of a trial limited to 10,000 people.

Truvada was launched in 2004, initially used in combination with other drugs as the basic treatment for people who have HIV, the virus that causes AIDS. It is primarily spread through sex.

Controversy arose in 2012 when the U.S. Food and Drug Administration approved Truvada to reduce the risk of getting HIV in the first place, for what’s called pre-exposure prophylaxis, or PrEP. It blocks the virus from making copies and taking hold. Critics warned that many gay men wouldn’t heed Truvada’s once-a-day schedule and complained of its high cost — roughly $1,500 a month.

Gilead offers a payment assistance plan to people without insurance that covers the full cost. Some cities and a few states — including Illinois, Massachusetts and Washington — also help cover costs. Activists have pressed Gilead to make its copay program more generous in light of its profits from Truvada.

“There’s no reason it has to cost so much,” said Krellenstein.

Gilead spokesman Ryan McKeel, in an email, said the company is reviewing the copay program.

“Like those in the advocacy community, we are committed to expanding access to Truvada for PrEP to as many people as possible,” he wrote.

In June, the FDA approved a generic version of Truvada, which is likely to push the price down, but it won’t be available in the U.S. for a few years.

The Truvada debate has taken many twists, as exemplified by the varying stances of the Los Angeles-based AIDS Healthcare Foundation — a leading HIV/AIDS service provider. In 2012, the group unsuccessfully petitioned the FDA to delay or deny approval of Truvada for preventive use. The foundation’s president, Michael Weinstein, belittled Truvada as “a party drug” and warned it would increase the spread of sexually transmitted infections by encouraging men to engage in sex without condoms.

But last year, the foundation, while still skeptical about some Truvada-related policies, urged Gilead to cut its price to make it more available.

“We have no dispute about its ability to prevent HIV transmission,” said spokesman Ged Kenslea. He noted that the organization’s 40 pharmacies across the U.S. handle many Truvada prescriptions.

By David Crary

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Middle-aged HIV-positive people have increased risk of ‘silent’ cerebral vascular disease linked to more severe health problems http://www.eatg.org/news/middle-aged-hiv-positive-people-have-increased-risk-of-silent-cerebral-vascular-disease-linked-to-more-severe-health-problems/ Tue, 09 Jan 2018 22:09:36 +0000 http://www.eatg.org/?post_type=news&p=7153

Prevalence of silent cerebral small-vessel disease (CSVD) – an important precursor to more serious neurocognitive conditions – is significantly higher among middle-aged HIV-positive people compared to controls in the general population, according to French research published in Clinical Infectious Diseases.

After controlling for age, blood pressure and other traditional risk factors, the investigators found that HIV was associated with a doubling in the risk of silent CSVD. HIV-positive people aged between 50 and 54 years had an especially elevated risk of the condition compared to their HIV-negative peers.

“Our study results revealed a high CSVD prevalence among middle-aged PLWHIVs [people living with HIV], despite cART [combination antiretroviral therapy]-sustained immunovirological control,” comment the authors. “We confirmed classical risk factors, e.g. hypertension and advancing age, and identified a specific HIV-associated factor, the nadir CD4-cell count.”

CSVD covers a range of abnormalities affecting blood vessels in the brain. In the general population, it is a major cause of cognitive impairment, frailty, altered gait, and is the second most important cause of dementia in the elderly.

Age and hypertension are known risk factors, but its association with HIV is unclear.

Investigators in France therefore designed a cross-sectional study involving middle-aged HIV-positive people, all of whom were doing well on antiretroviral therapy, and matched HIV-negative controls.

The aim was to compare the prevalence of CSVD and severe CSVD according to HIV infection status. MRI scanning – the acknowledged gold standard – was used to diagnose CSVD.

All the HIV-positive people were aged 50 years or older, were taking long-term antiretroviral therapy and had sustained virological suppression. Exclusion criteria included hepatitis C virus co-infection, drug or alcohol abuse and diagnosed neurological disease.

The final study population consisted of 456 people with HIV and 156 controls. Recruitment took place between 2013 and 2016.

People with HIV were younger than the controls (median age 56 vs 58 years, p = 0.001) and were also more likely to be male (85 vs 77%, p = 0.03).

Approximately two-thirds of the HIV-positive sample had been diagnosed before the introduction of effective antiretroviral treatment in 1996. Median nadir and current CD4 cell counts were 196 and 665 cells/mm3, respectively.

CSVD was detected in 52% of people with HIV compared to 36% of the controls. Severe CSVD was present in a fifth of the HIV-positive sample and 14% of HIV-negative people.

After adjustment for age, sex, alcohol use, blood pressure, lipids and history of cardiovascular disease, the investigators found that CSVD was significantly more frequent in people with HIV than controls (aOR = 2.3; 95% CI, 1.5-3.6); however, there was no association between HIV and the risk of severe CSVD.

Overall, the risk of CSVD increased with age.

Despite this, younger HIV-positive participants (50 to 54 years) had a five-fold increase in the risk of CSVD compared to age-matched controls; the risk was three-fold higher for HIV-positive individuals aged between 54 and 60.

Risk factors for CSVD in people with HIV included a nadir CD4 cell count below 200 cells/mm3 (aOR = 1.5; 95% CI, 1.0-2.3).

“Recent study results showing links between CSVD and cognitive and gait impairments, frailty and stroke in the general population and PLHIVs should prompt medical providers to search for CSVD in PLHIVs, using a brief MRI,” conclude the authors, who recommend that screening should be especially targeted at the over-60s.

By Michael Carter

Reference

Moulignier A et al. Silent cerebral small-vessel disease is twice as prevalent in middle-aged well-controlled cART-treated HIV-infected individuals than HIV-uninfected individuals. Clin Infect Dis, online edition, 2017.

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Diabetes in people with HIV over 50 overwhelmingly linked to old antiretrovirals, not age or body weight http://www.eatg.org/news/diabetes-in-people-with-hiv-over-50-overwhelmingly-linked-to-old-antiretrovirals-not-age-or-body-weight/ Tue, 09 Jan 2018 22:07:25 +0000 http://www.eatg.org/?post_type=news&p=7152

People with HIV over the age of 50 are more likely to have developed type 2 diabetes if they started antiretroviral treatment before 1999 or had a longer exposure to older antiretroviral drugs such as stavudine (d4T) or first-generation protease inhibitors such as nelfinavir or indinavir, according to a study of people receiving HIV care in British Columbia, Canada.

The onset of diabetes was much less likely in people aged 50 and over who started treatment from 2010 onwards, or who started treatment at a higher CD4 cell count, according to study findings published in the journal BMJ Open Diabetes Research & Care.

The findings are likely to provide reassurance that modern HIV treatment carries little risk of promoting the development of diabetes in people with HIV.

Diabetes mellitus, or type 2 diabetes, develops as a consequence of failures in the body’s ability to handle glucose. Production of insulin, the hormone which regulates glucose levels, may decline or cells may stop responding to insulin. When this happens glucose stays in the blood and is not taken up by cells for use as fuel. Over time, a high level of glucose in the blood leads to damage to small blood vessels, causing kidney damage, cardiovascular disease, lower limb damage and loss of sight.

Type 2 diabetes is more common in people who are obese and becomes more common with age. People with HIV are more likely to be diagnosed with type 2 diabetes but it is unclear to what extent HIV-related factors lead to a higher incidence of diabetes in people with HIV.

To investigate this question researchers at the St Paul’s Hospital, Vancouver, the University of British Columbia and the British Columbia Centre for Excellence in HIV/AIDS analysed the incidence of type 2 diabetes in people living with HIV who started treatment at St Paul’s Hospital up until July 31 2015. The cohort was predominantly male (89%) and white (83%) with a high prevalence of hepatitis C co-infection (43%) and AIDS-defining illness during the follow-up period (31%).

Patients were classified as having developed type 2 diabetes if at any time they had a blood sugar measurement above 11.1 mmol/L, or HbA1C > 6.5%, or had been prescribed antidiabetic medication or been recorded as diagnosed with diabetes.

Out of 1065 people who were aged 50 or over in July 2015, 235 people developed diabetes during an average of 13 years of follow-up. This represents an incidence rate of 1.61 new cases per 100 person-years of follow-up, 39% higher than the observed rate in the Canadian general population.

The study found no significant difference in the risk of developing diabetes by age at HIV diagnosis or age at treatment initiation, nor was developing diabetes associated with having hepatitis C virus antibodies or with injecting drug use. Sex, weight, or latest body mass index were not associated with the risk of developing diabetes.

In a further analysis restricted to people who had pre-treatment viral load measurements available (N = 1065), the development of diabetes was associated with several HIV-related factors including lower CD4 cell nadir, lower CD4 cell count at antiretroviral therapy (ART) initiation and ART initiation in the period 1997-2004. People who started treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen were less likely to develop diabetes (p = 0.003).

After controlling for other factors in a multivariable analysis, people who started treatment in the period 1997-2004 were almost 50 times more likely to develop diabetes compared to people who started treatment between 2005 and 2009 (adjusted odds ratio 48.9, 95% confidence interval 21.32-112.17).

In univariate analysis the duration of treatment with each of stavudine (d4T), zidovudine (AZT), lopinavir, indinavir and nelfinavir was associated with an increased risk of developing diabetes. In the case of stavudine, each 10% increase in time on the drug was associated with 39% increase in the risk of diabetes (OR 1.39, 1.27-1.53) while for nelfinavir, the risk increased by 63% for each 10% increase in time on the drug (OR 1.63, 1.19-2.24).

On average, people who developed diabetes spent 21% of their time on treatment taking a regimen that contained stavudine, whereas those who did not develop diabetes were exposed to the drug for 7% of the time they had taken antiretroviral treatment (p < 0.001). There were similarly pronounced differences in the duration of drug exposure between those who developed diabetes and those who did not develop diabetes for the nucleoside reverse transcriptase inhibitors (NRTIs) didanosine and zidovudine, and for the protease inhibitors indinavir, nelfinavir and lopinavir. People who developed diabetes had significantly less exposure to the newer antiretrovirals tenofovir, atazanavir and darunavir compared to those who did not, reinforcing the authors’ conclusion that diabetes in people with HIV is chiefly a consequence of first-generation antiretroviral treatment.

The effect of some protease inhibitors and NRTIs on the development of insulin resistance is well-established, say the authors, who report that the incidence of diabetes began to drop sharply after 2000, with only two diagnoses of diabetes in the entire clinic population between 2010 and 2015. This change coincides with the replacement of indinavir, nelfinavir and stavudine by NNRTIs and by the nucleotide analogue tenofovir in first-line antiretroviral treatment.

The authors say that it is important to monitor for type 2 diabetes in people with HIV, but stress that “the incidence of diabetes mellitus is likely to decline in PLWH [people living with HIV] who initiated ART more recently with the use of newer ART agents.”

By Keith Alcorn

Reference

Samad F et al. Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50. BMJ Open Diabetes Research & Care, 5: e000457, doi: 10.1136/bmjdrc-2017-000457, 2017.

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High prevalence of emphysema in middle-aged HIV-positive smokers http://www.eatg.org/news/high-prevalence-of-emphysema-in-middle-aged-hiv-positive-smokers/ Tue, 09 Jan 2018 22:00:04 +0000 http://www.eatg.org/?post_type=news&p=7151

HIV infection is associated with airway obstruction, French investigators report in AIDS. Middle-aged HIV-positive smokers were matched with HIV-negative smokers of the same sex and age. After controlling for potential confounders, the investigators found a significant association between HIV and airway obstruction, an association that persisted after controlling for history of previous serious lung disease. Smoking intensity was also a significant risk factor.

Lung function was measured using forced vital expiratory volume (FEV1) and forced vital capacity (FVC). FEV1 to FVC ratio was the primary outcome, and FEV1/FVC ratio below 0.70 and FEV1 below 80% was indicative of moderate to severe chronic obstructive pulmonary disease (COPD).

“We found that HIV infection was independently associated with lower FEV1/FVC ratios,” comment the authors. “HIV was also associated with an increased prevalence of airway obstruction.”

Small airway disease with emphysema results in airway obstruction and possibly COPD. There is an elevated prevalence of this condition in people with HIV, possibly related to high rates of smoking and previous HIV-related lung disease.

French investigators wished to establish a clear understanding of the risk of airway obstruction in HIV-positive people, especially those with multiple risk factors for the condition (older age, smoking and previous immune suppression).

They designed a case-controlled study involving 351 HIV-positive people and 702 age- and sex-matched controls.

Key inclusion criteria were age 40 years or above, smoking history of 20 pack-years or more, nadir CD4 cell count below 350 cells/mm3, and current CD4 cell count above 100 cells/mm3. Recruitment was restricted to current smokers or people who quit smoking within the previous three years. Individuals were excluded if they had had a lung infection within the previous two months.

The median age was 50 years and 17% of participants were women. Participants had smoked for a median of 30 pack-years and 91% of people living with HIV were current smokers compared with 67% of the HIV-negative control group (p < 0.0001). The majority of HIV-positive people (89%) had an undetectable viral load and the median current CD4 cell count was 573 cells/mm3.

The FEV1/FVC ratio was significantly impaired in people with HIV compared to the controls (0.74 vs 0.78, p < 0.0001). Airway obstruction was diagnosed in almost a fifth (19%) of HIV-positive people compared to 9% of controls (p < 0.0001).

HIV was strongly associated with lower FEV1/FVC values (p = 0.001), as was increasing age (p < 0.0001), increased smoking intensity (p = 0.007) and hepatitis C virus co-infection (p = 0.008). In contrast, female sex (p = 0.028) and increased body mass index (BMI) (p < 0.0001) were both associated with higher FEV1/FVC values.

The association between HIV and lower FEV1/FVC persisted after exclusion of people with a history of tuberculosis or pneumocystis (p = 0.006).

“PLWHIV [people living with HIV] are at increased risk of bacterial infection, pneumocystosis, tuberculosis, conditions which have all been associated with airway obstruction or emphysema,” write the researchers. “However, other mechanisms may also be implicated, as suggested by the persisting association between HIV and FEV1/FVC ratio after excluding study participants with a history of tuberculosis or pneumocystis infection.”

Restricting analysis to people with a nadir CD4 cell count between 200-350 cells/mm3 found an association between HIV and impaired FEV1/FVC values of borderline significance.

After taking into account potential confounders, there was also a strong association between HIV and airway obstruction (OR = 1.72; 95% CI, 1.08-2.73). Other risk factors were increasing age (OR = 1.77 per 10 years; 95% CI, 1.28-2.43) and intensity of tobacco use (OR = 1.11 per 5 pack-years increase; 95% CI, 1.03-1.20).

“Our study found a higher prevalence of measured airway obstruction in PLWHIV with a history of important immunodeficiency than in age and sex-matched control group smokers 40 years of age or more,” conclude the investigators.

By Michael Carter

Reference

Matkinson A et al. HIV is associated with airway obstruction: a matched controlled study. AIDS, 32: 227-32, 2017.

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Twice the rate of bone loss among ART-treated women than men http://www.eatg.org/news/twice-the-rate-of-bone-loss-among-art-treated-women-than-men/ Tue, 09 Jan 2018 21:57:26 +0000 http://www.eatg.org/?post_type=news&p=7150

Bone mineral density declines twice as quickly among HIV-positive women than HIV-positive men, according to Italian research published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The study is the largest ever analysis of long-term changes in bone mineral density (BMD) in HIV-positive people, over three-quarters of whom had an undetectable viral load at baseline. Several other modifiable risk factors were also associated with reductions in BMD, including hepatitis C virus infection (HCV), treatment with tenofovir (TDF), low vitamin D levels and lack of physical exercise.

“In a large cohort of HIV-infected men and women on long-term ART [antiretroviral therapy], BMD at both the femoral neck and lumbar spine, a significant predictor of fracture risk, declined twice as quickly among HIV-infected women compared to men, even after adjusting for other covariates,” write the authors. “Notably, the majority of our study population were less than 50 years old, and only 15% of female participants were menopausal at baseline and 24% during follow-up. Thus, with ageing and menopause, the rate of BMD decline among HIV-infected women is expected to be even more pronounced, as suggested by our sex*time differences.”

Declines in BMD during the first three years after starting ART are well described in the medical literature. However, rates of further bone loss and its risk factors are less clear. Investigators from the Modena Metabolic Clinic therefore designed a study involving 839 women and 1759 men taking long-term ART. BMD was measured every six to 12 months using dual-energy X-ray absorptiometry (DXA) scans for up to ten years. The investigators calculated annual rates of BMD decline in the hip (femoral neck) and lumbar spine and the factors associated with this. Their statistical models included demographics and HIV-related factors. A final model added an interaction between sex and duration of therapy (sex*time).

Participants had a minimum of two DXA scans (median five) during a median of five years of follow-up. All the participants were white, 82% were aged under 50 years, and 76% had an undetectable viral load at baseline. Approximately a third (30% of women and 27% of men) had co-infection with HCV. On entry to the study, 7% of men had low testosterone and 15% of women were post-menopausal, with a quarter of women categorised as post-menopausal at any time during follow-up.

Baseline mean BMD for the entire cohort was 1.138 for total body, 0.833 at the femoral neck and 1.055 at the lumbar spine.

In the initial analysis, BMD in the femoral neck declined significantly more among women than men (-0.0353, p < 0.0001), but there was no sex difference in changes to BMD in the lumbar spine.

Lower femoral neck BMD was also associated with longer exposure to tenofovir, increasing age, lack of physical activity, low testosterone or post-menopausal status, vitamin D insufficiency and co-infection with HCV. Protective factors included longer duration of treatment with an integrase inhibitor and higher body mass index (BMI).

When the investigators introduced a sex*time interaction into the model, annual changes in BMD were significantly greater among women than men at both the femoral neck (-0.00897 vs -0.00422, < 0.001) and lumbar spine (-0.0127 vs +0.00765, p < 0.001).

“In the largest and longest study of BMD changes among HIV-infected men and women to date, we have found nearly double the rate of BMD decline among HIV-infected women compared to men,” comment the investigators. “Our results highlight BMD losses among women, independent of menopause, effects that require future consideration in ART selection.”

They also note that several modifiable risk factors were associated with bone loss and that bone loss could potentially be slowed by, where appropriate, HCV therapy, vitamin D supplements, choice of HIV therapy and physical exercise.

“Low BMD is one of several risk factors for fracture,” conclude the researchers. “Therefore, the interventions likely to have the greatest impact in this ageing population are those that both attenuate BMD losses and minimize fracture risk through reduced falls.”

By Michael Carter

Reference

Erlandsom KM et al. Bone mineral density declines twice as quickly among HIV-infected women compared to men. J Acquir Immune Defic Syndr, online edition. DOI: 10.1097/QAI.0000000000001591 (2017).

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New ‘mini-pillbox’ device could deliver three HIV drugs in a single once-weekly dose http://www.eatg.org/news/new-mini-pillbox-device-could-deliver-three-hiv-drugs-in-a-single-once-weekly-dose/ Tue, 09 Jan 2018 21:50:27 +0000 http://www.eatg.org/?post_type=news&p=7148

A new oral device that is taken once a week in a capsule could deliver two or three antiretroviral drugs and significantly reduce the risk of missing does or of developing drug resistance, according to research published in Nature Communications.

The investigators describe their device as a ‘mini-pillbox’ – no larger than a normal pill capsule but containing a star-shaped structure that can dispense drugs for up to seven days. The star shape prevents the tiny device from passing out of the stomach into the small intestine until the drugs have been dispensed, at which point the device breaks up and passes into the intestines. The tiny device does not prevent food from passing through the digestive system.

The mini-pillbox can deliver up to six formulations (one per arm) but can only be used for once-weekly dosing when the daily dose is 50mg or less. The investigators used the integrase inhibitors dolutegravir and cabotegravir and the non-nucleoside reverse transcriptase inhibitor rilpivirine to test the device in pigs. The drugs were loaded onto polymer matrices which released the drugs slowly over the course of a week.

The pilot study showed that concentrations of each drug remained high, and in the case of rilpivirine at levels matching the peak seen with daily dosing, for at least one week. The speed at which the drugs were released could be altered by using a different polymer to hold the drug in place.

One drawback is that the delivery method is only suitable for drugs that are stable in stomach acid. Use of tenofovir alafenamide (TAF) had to be abandoned because only ten per cent of the drug remained in a stable form that could be metabolised after ten hours’ exposure to stomach acid.

The device is designed to overcome difficulties in dosing slow-release formulations orally. For people who do not want to receive a long-acting formulation by intramuscular injection, a once-weekly pill could be very attractive.

ViiV Healthcare is developing the combination of cabotegravir and rilpivirine as a long-acting formulation to be dosed every two months by subcutaneous injection.

The device would also be suitable for delivering drugs for pre-exposure prophylaxis (PrEP), say the study investigators. They modelled the potential impact of the mini-pillbox when used to deliver PrEP. Assuming a similar level of efficacy for the drugs used in the device as for tenofovir, they estimated that weekly PrEP would improve the efficacy of PrEP by 20% compared to daily PrEP, due to improved adherence.

The research was part-funded by the Bill and Melinda Gates Foundation and the United States National Institutes of Health.

By Keith Alcorn

Reference

Kirtane A et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nature Communications 9(2) 1-12, 2018.

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Dolutegravir and lamivudine potent and safe in people starting HIV therapy for the first time http://www.eatg.org/news/dolutegravir-and-lamivudine-potent-and-safe-in-people-starting-hiv-therapy-for-the-first-time/ Tue, 09 Jan 2018 21:46:18 +0000 http://www.eatg.org/?post_type=news&p=7147

The two-drug antiretroviral combination dolutegravir and lamivudine is virologically effective and safe in people starting HIV therapy for the first time, according to US research published in the online edition of Clinical Infectious Diseases.

The phase 2 pilot study recruited 120 antiretroviral-naïve adults. After 24 weeks of treatment, 90% of participants had viral suppression and none of the participants discontinued therapy because of side-effects. There were few virological failures, and these were linked to poor adherence.

Modern antiretroviral therapy usually consists of three separate drugs and is highly effective. Safety and cost considerations mean there is interest in identifying effective two drug combinations. Dolutegravir and lamivudine performed well in a small study with high rates of virological suppression over 96 weeks.

Investigators in the US wanted to build on this research. They therefore designed a pilot, phase 2, open-label study (ACTG A5353) involving adults with a viral load between 1000 and 500,000 copies/ml who were starting antiretroviral therapy for the first time. Key exclusion criteria were infection with hepatitis B virus and antiretroviral resistance.

Viral load was measured at regular intervals over 24 weeks. The main outcome was viral suppression (below 50 copies/ml) at week 24. Virological failure was defined as a viral load above 400 copies at weeks 16/20 or above 200 copies/ml at week 24. People experiencing virological failure underwent therapeutic drug level monitoring and resistance testing. Data were gathered on adherence and safety.

The participants had a median age of 30 years and 87% were male. Median baseline viral load and CD4 cell count were 40,000 copies/ml and 387 cells/mm3, respectively.

Seven people were lost to follow-up or withdrew from the study before week 24.

Overall, 108 people (90%) had an undetectable viral load at week 24. Rates of viral suppression were similar for people with baseline viral loads above and below 100,000 copies/ml (90 vs 89%).

Three people experienced virological failure. Drug level monitoring showed undetectable levels of dolutegravir, therefore suggesting poor treatment adherence.

One person with virological failure developed the M184V mutation, which confers resistance to lamivudine, and also the R263R/K mutation, potentially limiting the effectiveness of dolutegravir.

Adherence was excellent, with 90% reporting taking all their doses.

The median increase in CD4 cell count over the study was 167 cells/mm3. Ten people reported grade 3/4 adverse events, but only two were considered possibly related to therapy (grade 3 reduction in creatinine clearance and grade 3 palpitation). There were also two cases of mild rash. None of the participants stopped treatment early because of side-effects.

“The two-drug regimen of dolutegravir and lamivudine was generally safe and well-tolerated consistent with the known favorable toxicity profiles of these two agents,” comment the authors. “No participant discontinued the regimen because of adverse events. Notably, the combination of dolutegravir and lamivudine has the potential to be co-formulated into a single pill without dietary restrictions. Antiretroviral regimens must be well-tolerated and convenient to support long-term adherence.”

On the basis of current drug prices, the investigators calculated that widespread use of this two-drug combination in the US could save at least $3 billion over five years.

“The week 24 results of the…study showed that the two-drug antiretroviral regimen of dolutegravir and lamivudine was virologically potent and generally safe and well-tolerated in individuals with pre-treatment HIV-1 RNA up to 500,000 copies/ml,” conclude the researchers. “Fully-powered phase 3 studies in progress will provide needed comparative data versus dolutegravir-based three-drug therapy in treatment-naïve individuals.”

By Michael Carter

Reference

Taiwo BO et al. ACTG A5353: a pilot study of dolutegravir plus lamivudine in initial treatment of HIV-1-infected participants with HIV-1 RNA < 500,000 copies/ml. Clin Infect Dis, online edition, 2017.

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DATE CHANGE for the 3rd Ageing with HIV Conference http://www.eatg.org/news/date-change-for-the-3rd-ageing-with-hiv-conference/ Thu, 04 Jan 2018 15:12:51 +0000 http://www.eatg.org/?post_type=news&p=7138 The 3rd Ageing with HIV conference that was scheduled to be held on the 22-25 March 2018 has been postponed to 3-6 May 2018. The venue (Kyiv, Ukraine) and the overall timing (opening on Thursday night and closing Sunday noon) of the meeting however remain the same. We have decided to move the conference due to an unexpected scheduling conflict and following what we believe to be in the best interest of the attendees and sponsors. We would like to express our apologies for this sudden change and we hope that any inconvenience this date change may cause can be minimised by this early notice.

How to Apply:

You are welcome to apply to the conference by filling in the application form online at https://www.surveymonkey.com/r/BZV8QXL (the link remains the same as communicated earlier). Please reply in English and be as detailed as possible in your answers to all of the questions on the form. The new deadline for submitting your application is Monday, 12th of February 2018, 23:59 Central European Time.  Please note that those who have already applied will be contacted individually to confirm their interest and availability to attend the conference on this new date. You do not need to re-apply if you already have filled in the online form.

We kindly ask you to please share this notification with your networks.

About the conference:

As part of the Ageing with HIV Project, the European AIDS Treatment Group (EATG) is organizing a conference on the topic “New Challenges and Unmet needs of people Living and Ageing with HIV/AIDS Aged 18-50 – Quality of Life and Preventive Healthcare”. The conference will take place at the Alfavito Hotel in Kyiv, Ukraine. The working language of the conference is English.

By bringing together the patients’ community, researchers, healthcare providers and other key actors working in the domain of ageing and HIV it is expected that the conference will provide an overview of the latest research on the medical, psychological and social aspects of living and ageing with HIV/AIDS and the identification of key advocacy needs and priorities in this domain. This 3rdand final conference of the Ageing Project will focus on quality of life, health outcomes and preventive healthcare targeting People Living with HIV aged 18 to 55 years old from different key affected groups.

More information about the conference and the Ageing project can be found on the (EATG) Ageing with HIV Website at http://www.ageingwithhiv.org/

Selection Criteria:

Please note that the conference is open only to selected candidates. All applicants will be informed of the selection outcome two weeks after the deadline.

  • General criteria: Motivation to attend the conference, understanding of HIV in general/willingness to learn about HIV and ageing, knowledge and working experience on the conference topic, ability to convey meeting outcomes & findings to a wider audience.
  • Consideration: Geographic region
  • Essential requirement: To be able to actively participate for the full duration of the meeting

Conference fee and scholarships:

Accepted candidates will have free access to the conference sessions. A limited number of successful candidates will be granted full (travel, accommodation, meals) or partial (accommodation, meals) scholarships for their participation. Please state on the registration form which type of support you wish to be considered for.

Thematic Webinars:

Two webinars on topics related to the conference are planned in conjunction to the conference (dates to be confirmed). You are strongly encouraged to attend these webinars. For more information, please see http://www.ageingwithhiv.com/thematic-webinars.

If there are any questions about the conference, please do not hesitate to contact the EATG office at projects@eatg.org.

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Give another push for EMIS and ECHOES! http://www.eatg.org/news/give-another-push-for-emis-and-echoes/ Wed, 03 Jan 2018 22:35:17 +0000 http://www.eatg.org/?post_type=news&p=7137 Both European surveys: EMIS2017 (for MSM) and ECHOES (for community health workers working with MSM) are still open. Both surveys are available in several different European languages.

ECHOES: We invite Community Health Workers who provide sexual health and support services for MSM in the EU and neighbouring countries to participate at www.echoessurvey.euThe deadline has been extended until 31 January 2018. Don’t forget that anyone who provides sexual health support to MSM in community settings (i.e. not in a hospital or a clinic) can participate in ECHOES – whether you are a medically trained professional, a counsellor or a lay-person, whether the work is done on a full-time, part-time or occasional basis, and whether the work is done on a paid or voluntary basis.
EMIS: We invite all men who have sex with men to contribute to this important survey about relationships, sex life, risks and precautions, and use of health services. You can access it here until 17 January 2018.

You are welcome to disseminate this information in your networks.

Both surveys are part of the ESTICOM project, please read more at https://www.esticom.eu/.

EATG has been a key partner in both projects. We have also used the data resulting from the previous round, EMIS2010, extensively to support our advocacy work over these years. ECHOES is new but equally important, and it will be followed up with a series of training sessions for community health workers across Europe to make them even better in what they do.
By participating, and by making sure that the survey reaches the widest possible audience of gay men and other men having sex with men, we can generate even better and more relevant datasets for our future work.
Please address all questions and comments to Maria Dutarte (maria.dutarte@eatg.org) or Tamás Bereczky (tamas.bereczky@eatg.org).
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Are you following the EATG 4 Women Portfolio? http://www.eatg.org/news/are-you-following-the-eatg-4-women-portfolio/ Tue, 02 Jan 2018 21:52:26 +0000 http://www.eatg.org/?post_type=news&p=7134

EATG has been operating the EATG4WOMEN portfolio for only a few months, and it is already one of the most successful initiatives.

Join the Facebook group for the latest updates.

EATG4WOMEN REPORT

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EATG Christmas Newsletter http://www.eatg.org/news/eatg-christmas-newsletter/ Wed, 27 Dec 2017 21:40:48 +0000 http://www.eatg.org/?post_type=news&p=7130 The year may be ending, the fight against HIV is not

What a tumultuous year 2017 has been! EATG has grown again, more projects than ever, another STEP-UP cohort graduated, we have produced a series of amazing webinars, and there will be even more in 2018! Executive Director Koen Block wishes you all a happy holiday season and a good start into the New Year.

Click here to read the EATG Christmas Newsletter, highlighting the major achievements of the organisation in 2017.

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Your feedback matters: Post-Testing Week 2017 evaluation survey http://www.eatg.org/news/your-feedback-matters-post-testing-week-2017-evaluation-survey/ Mon, 25 Dec 2017 17:48:31 +0000 http://www.eatg.org/?post_type=news&p=7121 If you haven’t already, you are kindly invited to fill out the Post-European HIV-Hepatitis Testing Week 2017 evaluation survey.

Even if you did NOT do Testing Week activities, you are still invited to fill out the first portion of the survey!

Deadline for completion of the survey is 31 January 2018.

The survey can be accessed here.

For more information, click here.

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Epidemiological update: hepatitis A outbreak in the EU/EEA mostly affecting MSM http://www.eatg.org/news/epidemiological-update-hepatitis-a-outbreak-in-the-eueea-mostly-affecting-msm-2/ Mon, 25 Dec 2017 17:47:17 +0000 http://www.eatg.org/?post_type=news&p=7129 Since the last epidemiological update on this multi-country hepatitis A outbreak published on 29 September 2017, 22 EU/EEA countries (Austria, Belgium, Croatia, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Luxembourg, Malta, the Netherlands, Norway, Portugal, Slovenia, Spain, Sweden and the United Kingdom-England & Wales) have reported 950 new outbreak-confirmed cases. Outbreak-confirmed cases are EU/EEA residents with laboratory-confirmed hepatitis A virus (HAV) genotype IA and a sequence with ≥99.3% homology to one of the three HAV genotype IA outbreak strains (VRD_521_2016; RIVM-HAV16-090; and V16-25801) based on overlapping fragments at the VP1-2a region.

Read the full ECDC update here.

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The unexpected success of NRTIs in second-line treatment http://www.eatg.org/news/the-unexpected-success-of-nrtis-in-second-line-treatment/ Mon, 25 Dec 2017 17:46:41 +0000 http://www.eatg.org/?post_type=news&p=7122 Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. A study, published in The Lancet Infectious Diseases, assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings.

The full study is available here.

An accompanying comment can be accessed here.

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Anal high-risk HPV infection more common in HIV-positive MSM http://www.eatg.org/news/anal-high-risk-hpv-infection-more-common-in-hiv-positive-msm/ Mon, 25 Dec 2017 17:45:25 +0000 http://www.eatg.org/?post_type=news&p=7127 In a new study published in the Journal of Infectious Diseases, Pragna Patel, MD, MPH, and her colleagues set out to characterize the epidemiology of human papillomavirus (HPV) infection in men who are infected with HIV. HPV infection can lead to anal cancer and it is estimated that men who have sex with men (MSM) are 20 times more likely to develop anal cancer than heterosexual men. In addition, the authors note that HIV-infected MSM are more likely to develop anal cancer than HIV-uninfected MSM, with incidence rates being approximately 80 times higher for HIV-infected MSM in comparison to HIV-uninfected men.

Furthermore, studies have shown that HIV-infected MSM are less likely to clear anal HPV infection, particularly for HPV type 16. This is particularly concerning as failure to clear HPV types 16 and 18 is a known risk factor for developing anal cancer. Although vaccination can potentially prevent anal high-risk HPV infections, current vaccination protocols and clinical guidelines would certainly benefit from in-depth epidemiological studies. Therefore, Dr. Patel and her colleagues sought to fill in this missing link.

A total of 700 HIV-positive patients from 7 clinics in 4 cities were enrolled in the Study to Understand the Natural History of HIV/AIDS in the ERA of Effective Therapy (SUN study) from March 2006 until June 2006. Of the 700 patients enrolled in the SUN cohort, 525 were men and 499 had an HPV positive result during the baseline visit. The men were asked to self-report on their sexual behavior and were thus classified as either MSM (81%) or men who have sex with women (MSW) (19%). Most of the participants were receiving highly active combination therapy (cART).

The investigators found that the anal prevalence of HPV was 95% for MSM and 59% for MSW, with high-risk HPV types detected in 85% of MSM and 48% of MSW. The most common types of HPV found among both MSM and MSW was 16 and 6. In addition, when compared to HIV-infected MSW, MSM had an increased likelihood of having abnormal anal cytology. The investigators attributed these results to sexual behavior differences between MSM and MSW, with MSM reporting a greater number of sexual partners than MSW.

Although the study results showed that MSM had higher incidence and prevalence of anal HPV infection, they determined that clearance and persistence rates of high-risk HPV types were not different between the 2 groups.

Some limitations of the study include the lack of an HIV-negative group of men for comparison purposes as well as an inability to quantify the number of HPV virions detected. In addition, the SUN study only collected anal specimens on a yearly basis, which could lead to an overestimation of HPV incidence. The investigators noted that they were also unable to distinguish between an episode of HPV re-infection and failure to clear an HPV infection.

Nonetheless, this work sheds light on the prevalence of HPV in HIV-infected men which can help shape future screening protocols and recommendations in this population.

By Samar Mahmoud

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Why finding new HIV targets takes so long: Some basics about basic research http://www.eatg.org/news/why-finding-new-hiv-targets-takes-so-long-some-basics-about-basic-research/ Mon, 25 Dec 2017 17:36:37 +0000 http://www.eatg.org/?post_type=news&p=7126 Although great strides have been made at combating human immunodeficiency virus, leading to better quality of life and a longer life expectancy for those living with the virus, significant problems remain.

As of 2016, 36.7 million people worldwide were living with the virus. Of those people, 20.9 million accessed antiretroviral therapy, the lifesaving cocktail of drugs that slows the progression of the disease.

While this is an improvement from the previous year’s numbers, this still only covers about 57 percent of people infected.

My colleagues and I, in Michael Summers’ lab, work to determine the structures of HIV biomolecules in order to learn more about how those structures affect the function of the virus. We use this information to inform others seeking to design new HIV treatments.

As an AIDS basic researcher, I have experienced firsthand why lab work takes so long to reach actual AIDS patients.

High mutation rates complicate treatment

Treatment of HIV is complicated by a high mutation rate, which causes the virus to quickly develop resistance to antiretroviral therapies. This necessitates using a cocktail of drugs that each target a different step in the viral replication cycle, as it is less likely for the virus to simultaneously develop resistance to multiple drugs at the same time.

This combination of drugs initially resulted in large numbers of pills taken on a complex schedule, making it difficult for patients to keep track. Unfortunately for those with the virus, lack of adherence to the antiretroviral schedule increases the likelihood that the virus will develop resistance to the medications, which can complicate future treatment.

New therapies use combination pills that alleviate some of the strain associated with the treatment schedule, resulting in more patients adhering to their treatment regimen. Despite this, the World Health Organization estimates that only 74 percent remain in antiretroviral therapy after 12 months.

The WHO also found drug resistance in 10-22 percent of certain populations who had never received antiretroviral therapy, indicating that some people are initially infected with resistant strains of the virus. In order to combat this drug resistance, new classes of drugs focusing on different parts of the HIV replication cycle are needed.

The drug discovery process

Early development of antiretroviral drugs, such as AZT, used known compounds against the virus in the hopes of finding one with a therapeutic effect. This pathway to drug design requires screening thousands of drugs in an inefficient process.

To speed the process, researchers began developing rational drug design methods, which use computer modeling and information about the biological targets to create drugs aimed at stopping a specific viral process.

However, before this applied research can find new therapies, basic research must first identify and examine the potential targets. Basic research aims to expand the knowledge base or understand a phenomenon without immediate commercial applications. The exploratory nature of basic research makes it difficult to predict the outcomes, which often leads to unexpected results that redirect the path of the research. While exciting, these twists and turns often cause delays and require additional investigation, and can sometimes masquerade as mistakes.

Why HIV is different

Many people in our lab have worked to solve the structure of part of the HIV genome, which is composed of RNA instead of the DNA associated with most genomes. RNA has more flexibility than DNA, and thus has the ability to form unique structures.

The genome, or part of the virus that holds all the instructions to make a new virus, has two functions in an infected cell. As a single copy, or monomer, it codes for viral proteins that allow assembly of a new virus. However, the genome can also self-associate, making a two-copy structure called a dimer that is packaged into a new virus. There, it serves as the genetic blueprint for the virus in the next infected cell.

One of the major questions for early researchers was how the genome switches between the two conformations. The working hypothesis was than an equilibrium existed between the two states, allowing the genome to switch from one form to another. One of the graduate students in my lab, Sarah Monti, spent years working on the structure of the monomer, trying to find the conditions to stabilize the structure.

She used the genome sequence published in the HIV Sequence Compendium, a database of HIV sequences. When she went to recheck the sequence at a later point, she found that the sequence had changed slightly. At first fearing she had used the wrong sequence, she and another graduate student, Thao Tran, began digging into the matter further.

They found work from other labs that suggested that three different RNAs are made by the infected cell, each varying by a single building block at the beginning of the molecule. Sarah’s work with her collaborators found that these RNAs have different roles in the virus and are the root cause of the difference in function.

Further work with the genome has determined that the monomer and dimer molecules have unique structures that provide two targets for potential drugs. Disrupting either molecule could lead to a new class of therapeutics in the fight against HIV.

What was originally thought to be a mistake changed the way we think about RNA structures and rewrote the paradigm of how the HIV genome functions.

Unexpected results can lead to unexpected benefits

In my own work, a team and I sought to confirm a proposed mechanism about how the HIV virus assembles. Because we used a technique that limited the size of the molecules, we simplified the experiment by removing a part of molecule deemed unimportant for the process by other researchers.

Our experiments had results that differed from what the scientific literature suggested we should see. We repeated the experiments to ensure that we had completed them correctly. Then, we tried other experiments to probe the process further. After more than a year of exhausting other possible explanations, we concluded that the part we had removed was indeed important – a conclusion that has led to additional questions about the mechanism of the process.

Because scientific studies are published after careful consideration of the data and interpretation of the results, it’s difficult to know just how many breakthroughs started as experiments seeking something else.

Although basic research takes time and often does not go as intended, the same fundamental qualities that can lead to frustration can also provide unexpected rewards as well as the exhilaration of discovery. Basic science research of HIV often yields more results beyond the intended understanding of viral processes.

By Christy Gaines

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Selective suppression of inflammation could deplete HIV and control HIV activation http://www.eatg.org/news/selective-suppression-of-inflammation-could-deplete-hiv-and-control-hiv-activation/ Mon, 25 Dec 2017 17:08:47 +0000 http://www.eatg.org/?post_type=news&p=7123 A class of anti-inflammatory drugs already FDA-approved for rheumatoid arthritis could “purge” the reservoir of infected immune cells in people infected by HIV, according to new research.

When culturing cells from HIV-infected individuals, researchers found the medications tofacitinib and ruxolitinib block viral production from infected cells, prevent transmission to bystander cells, and decay the viral reservoir. The results were published in PLOS Pathogens.

“One of the major impediments to an HIV cure is the reservoir,” said the study’s senior author Rafick-Pierre Sékaly, PhD, the Richard J. Fasenmyer Professor of Immunopathogenesis, co-director of the Center for AIDS Research Proteomics and Systems Biology Core, and professor of pathology at Case Western Reserve University School of Medicine. “These are a very small number of immune cells that have the virus integrated into their genomes. These cells are completely undetectable by the immune system because the virus is dormant. But as soon as you stop treatment, the virus reactivates. Our results show you can kill these reservoir cells if you treat them with Jak inhibitors.”

The new study included 37 people infected by HIV, but who have controlled the virus with antiretroviral drugs. The size of their residual reservoir – the number of cells with HIV integrated into their DNA – was linked to the activity of Jak enzymes in the cells. The research suggests blocking Jak enzymes could, in effect, impose a drought on the HIV reservoir. Laboratory experiments confirmed that Jak inhibitors prevent HIV spread to nearby, healthy cells.

Jak inhibitors block key pro-inflammatory cytokines that are dysregulated in certain diseases including autoimmune disorders such as rheumatoid arthritis. In blocking these inflammatory cytokines, Jak inhibitors restore the inflammatory state to a “normal” level observed in individuals without an inflammatory disorder.

Sékaly’s foundational research into HIV reservoir persistence made him a natural collaborator for researchers at Emory with expertise in small molecule Jak inhibitors. Co-corresponding author on the study is Raymond F. Schinazi, PhD, DSc, a Frances Winship Walters Professor of Pediatrics and Director of the Laboratory of Biochemical Pharmacology at Emory University. Schinazi is also the director of the HIV Cure Scientific Working Group at the Emory University Center for AIDS Research. One of the study’s three first authors, Christina Gavegnano, PhD is an Assistant Professor in Dr. Schinazi’s group. Schinazi and Gavegnano previously reported that Jak inhibitors demonstrate antiviral potency in human immune cells, and that ruxolitinib can ameliorate HIV-associated encephalitis in a mouse model.

The researchers hope their collaborative study could result in a new approved indication for Jak inhibitors to treat HIV infected individuals. Said Schinazi, “Our results strongly suggest that monitoring and suppressing inflammation with Jak inhibitors will impact HIV reservoirs not only systemically, but also in the central nervous system where the virus hides.”

A key safety feature of Jak inhibitors in the study is that they are not globally immunosuppressive, but instead immunomodulatory. Said Sékaly, “Our results show how Jak inhibitors do not prevent the reservoir cells from responding to new infections.”

The PLOS Pathogens paper showed Jak inhibitors do not block functional immune responses to HIV, or normal immune cell function. These findings are mirrored by data collected in humans where global immunosuppression is not reported with Jak inhibitors. This mechanism of action is unique due to the drugs’ apparent specificity for HIV-infected cells, unlike global immunosuppressive agents used in transplants, which blunt all activation and result in reduced functional immunity.

Since Jak is overactive in HIV-infected cells, Jak inhibitors are able to specifically target inflammatory cytokines in the cells that cause them to activate and “reseed” nearby cells. HIV requires cellular activation to replicate efficiently. Blocking key inflammatory cytokines in HIV-infected cells with a Jak inhibitor creates an environment where the virus simply cannot replicate because it cannot properly activate the cell. The unique mechanism of action allows Jak inhibitors to block viral replication in infected cells, reduce the lifespan of reservoir cells (key markers such as Bcl-2 are down-regulated), and block expansion of the viral reservoir.

Explained Gavegnano, “Jak inhibitors are unique since they are highly selective agents that keep the lid on smoldering infection through anti-inflammatory properties. If the lid is on the smoldering fire long enough, it is our hope that the fire will be extinguished.”

The study results have strengthened rationale for an ongoing, AIDS Clinical Trial Group (ACTG) Phase 2a multi-site trial to evaluate the safety, tolerability and efficacy of ruxolitinib in HIV-infected individuals. “We are rigorously evaluating the effect of Jak inhibitors on key events that prevent eradication of HIV in culture, animal models and humans,” said Gavegnano. “We are also carefully monitoring safety.It is important to evaluate these agents from every possible angle, to ensure that we are delivering a safe and effective treatment. Our data to date provides reason to explore the indication of HIV for Jak inhibitors carefully. We look forward to understanding how blocking residual inflammation in HIV-infected cells can impact the ultimate goal of a cure.”

###

The study was made possible by multiple grants to Sékaly from the National Institute of Mental Health and the National Institute of Allergy and Infectious Diseases. Schinazi’s team is funded by the National Institute of Mental Health and Emory’s Center for AIDS Research.

PLOS Pathogens, Gavegnano et al. “Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors.” doi: 10.1371/journal.ppat.1006740

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Team develops more accurate tool to track new HIV infections http://www.eatg.org/news/team-develops-more-accurate-tool-to-track-new-hiv-infections/ Mon, 25 Dec 2017 14:58:33 +0000 http://www.eatg.org/?post_type=news&p=7124 Population-based model would benefit research, public health initiatives worldwide

Researchers at the Duke Human Vaccine Institute have led an effort to develop a more accurate way to gauge the incidence of HIV infections in large populations, which will improve research and prevention strategies worldwide.

The new method more correctly identifies new vs. long-standing infections — an important distinction for determining where to target public health measures and research, and for evaluating whether interventions are successful at reducing HIV transmission.

“Recent advances — including effective anti-retroviral drugs that both treat and prevent HIV infections — have changed the landscape in the HIV field,” said senior author Georgia Tomaras, Ph.D., professor in the Department of Surgery and director of research at Duke Human Vaccine Institute. The study is published online Dec. 21 in the journal JCI Insight.

“Improved methods for classifying recent infection from older infections are critically needed to help identify the most effective prevention strategies,” Tomaras said.

Tomaras and colleagues worked to develop a way to measure HIV incidence that takes into account the unique features of the current epidemic while also capitalizing on recent insights into how the virus and the body interact during the early phases of infection.

The result was an assay that identifies new combinations of naturally occurring antibody biomarkers, resulting in a promising set of four biomarkers that could be used. The new assay has a longer, and thus more accurate, time-period that constitutes recent infection, and fewer false classifications.

“Having a more accurate HIV incidence test could substantially reduce costs for researchers, because they would need a much smaller sample size to enroll in studies,” Tomaras said.

“Additionally, from a public health standpoint, a more accurate HIV incidence test would help identify hot spots of recent infections, so that prevention efforts could be better targeted to where outbreaks are happening,” said Kelly Seaton, Ph.D., lead author on the study.

Watch a short video here.

Journal Reference:

  1. Kelly E. Seaton, Nathan A. Vandergrift, Aaron W. Deal, Wes Rountree, John Bainbridge, Eduard Grebe, David A. Anderson, Sheetal Sawant, Xiaoying Shen, Nicole L. Yates, Thomas N. Denny, Hua-Xin Liao, Barton F. Haynes, Merlin L. Robb, Neil Parkin, Breno R. Santos, Nigel Garrett, Matthew A. Price, Denise Naniche, Ann C. Duerr, Sheila Keating, Dylan Hampton, Shelley Facente, Kara Marson, Alex Welte, Christopher D. Pilcher, Myron S. Cohen, Georgia D. Tomaras. Computational analysis of antibody dynamics identifies recent HIV-1 infection. JCI Insight, 2017; 2 (24) DOI: 10.1172/jci.insight.94355
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Anti-virus protein in humans may resist transmission of HIV-1 precursor from chimps http://www.eatg.org/news/anti-virus-protein-in-humans-may-resist-transmission-of-hiv-1-precursor-from-chimps/ Mon, 25 Dec 2017 14:54:26 +0000 http://www.eatg.org/?post_type=news&p=7128 Cross-transmission of HIV-1 precursor may have started in people with unstable forms of the protein

In humans, an anti-virus protein known as APOBEC3H may defend against cross-species transmission from chimpanzees of the virus that gave rise to HIV-1. Zeli Zhang of Heinrich-Heine-Universität Düsseldorf, Germany, and colleagues present this finding in a new PLOS Pathogens study.

APOBEC3H, or A3H, is one of several anti-viral proteins known as A3s that repress replication of lentiviruses, a genus of viruses that includes HIV-1. HIV-1 originated when chimpanzee strains of simian immunodeficiency virus (SIVcpz) spread to humans. However, few studies have explored the effects of human A3s on SIVcpz.

In the new study, Zhang and colleagues investigated how A3 proteins in both chimpanzees and humans impact SIVcpz. They infected cells from a laboratory cell line with SIVcpz strains in the presence of different A3s. Using a novel method, the SIVcpz viruses had been genetically modified to emit light under certain conditions, enabling the researchers to quantify their infectivity in the cells.

The researchers found that a human A3 protein known as A3H haplotype II strongly inhibited SIVcpz. This was due to A3H’s resistance to SIVcpz proteins known as Vifs, which fight back against A3s. A3H can occur in different forms, and other forms of human A3H demonstrated similar activity against SIVcpz.

Using genomic sequencing data from the Great Ape Genome Project, the research team also found that human A3H has a wider range of different possible forms than does chimpanzee A3H. Further experiments showed that Vif proteins from SIVcpz and gorilla SIV were capable of degrading chimpanzee A3H, but not A3H haplotype II.

Overall, these findings suggest that human A3H may protect against transmission of SIVcpz from chimpanzees to humans. Thus, transmission of SIVcpz strains that gave rise to HIV-1 may have begun in people with unstable forms of A3H.

Journal Reference:

  1. Zeli Zhang, Qinyong Gu, Marc de Manuel Montero, Ignacio G. Bravo, Tomas Marques-Bonet, Dieter Häussinger, Carsten Münk. Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans. PLOS Pathogens, 2017; 13 (12): e1006746 DOI: 10.1371/journal.ppat.1006746
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Ireland: Gilead withdraws challenge to generic HIV drug http://www.eatg.org/news/ireland-gilead-withdraws-challenge-to-generic-hiv-drug/ Thu, 21 Dec 2017 04:48:34 +0000 http://www.eatg.org/?post_type=news&p=7116 Gilead has dropped its appeal against the High Court’s refusal to grant an injunction against generic manufacturers

Pharmaceutical giant Gilead, which manufactures the HIV anti-retroviral drug Truvada, has withdrawn its appeal against the High Court’s refusal to grant an injunction against generic manufacturers.

Gilead has generated almost $14 billion globally in recent years from sales of Truvada, which is used as a pill (pre-exposure prophylaxis – PrEP) to help prevent the contraction of HIV.

PrEP was made available for purchase in Ireland earlier this month along with a generic version of the medication.

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.

Gilead 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 SPC. The court rejected its application for a provisional injunction which would have blocked Mylan and Teva until a full trial.

Gilead has confirmed to the Court of Appeal that it has withdrawn its appeal of the High Court’s decision.

David Delaney, European director of Mylan said “it’s fantastic news for patients in Ireland”.

“Lower prices means greater access for patients, we had heard anecdotally of patients sharing medicine and not really sticking to the regime,” Mr Delaney said.

Illegal purchasing

“We hope that this will also decrease the illegal purchasing of medicine in Ireland. There are a number of websites in Ireland and the UK that offer this medicine, whether that’s a genuine source or not, people go to these websites and purchase the product for a certain price and I think to some extent can be taking a bit of a chance.”

“Mylan welcomes the withdrawal of Gilead’s appeal of the decision to refuse a preliminary action as it is set to both increase patient access to this important medicine and decrease the estimated €24 million the Health Service Executive spends on Truvada,” a statement from the pharmaceutical company said.

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

More than 500 new cases of HIV were diagnosed in Ireland last year. Rates have been rising steadily since 2011, with the rate of new infections increasing significantly within the past two years.

Nearly half of the new HIV cases resulted from sex between men. Nearly a fifth came after heterosexual sex. Just four per cent of cases are reported from people who inject drugs.

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Treatment regimens and recommendations for HIV/HCV coinfection http://www.eatg.org/news/treatment-regimens-and-recommendations-for-hivhcv-coinfection/ Thu, 21 Dec 2017 04:45:19 +0000 http://www.eatg.org/?post_type=news&p=7118 Challenges in Treatment of HIV and HCV Coinfection

Coinfection with HIV and hepatitis C virus (HCV) is common. In the United States, up to one-third of those with HIV are coinfected with HCV and one-third of those with HCV are coinfected with HIV.1,2 The high prevalence of HIV and HCV coinfection is likely the result of shared modes of transmission for both types of infection, such as intravenous drug use, sexual contact, or mother-to-child transmission.3

“We need to be aggressively treating everyone with HCV, including and especially patients who are coinfected with HIV, because we know that patients who are coinfected are at higher risk for more rapid progression of liver disease,” Lisa Chirch, MD, FIDSA, Associate Professor of Medicine in the Infectious Diseases department at UConn Health in Connecticut, told Infectious Disease Advisor. Liver cirrhosis will develop in approximately one-third of patients with HCV and HIV coinfection within 20 years. Additionally, patients with coinfection are 3 times more likely to have progression to decompensated liver disease or cirrhosis than are patients with HCV infection alone.4

Previously, the only therapies available for HCV infection were pegylated interferon and ribavirin, which were often ineffective at disease control and poorly tolerated. The development of next-generation direct-acting antivirals (DAAs) for HCV has led to significantly improved sustained virologic response rates and better tolerability in people with both HIV/HCV coinfection and those with HCV alone.4 Consequently, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidelines for HCV treatment recommend that people with HCV and HIV coinfection be treated similarly to those with HCV monoinfection.5

Whereas the new oral DAAs make viral suppression of HCV an achievable goal in patients with HCV/HIV coinfection, the simultaneous use of HIV antiretroviral therapy (ART) presents new challenges regarding drug-drug interactions (DDIs). Infectious Disease Advisor spoke with Dr Chirch and with Oluwaseun Falade-Nwulia, MBBS, MPH, Assistant Professor of Medicine in the Infectious Diseases department at Johns Hopkins Medicine in Maryland, about the management of DDIs in patients receiving treatment for HIV and HCV coinfection.

Resources to Identify DDIs in HIV and HCV Regimens

“Providers who treat patients with HIV and HCV coinfection need to be aware of DDIs between HIV and HCV medications to prevent bad outcomes that are potentially avoidable,” Dr Falade-Nwulia said.

“We have so many options for HCV therapy now that we are in a position to treat any [patient coinfected with] HIV/HCV,” she added. However, with numerous potential HIV and HCV drug combinations, many DDIs are possible. Staying current on what DDIs may occur with all HIV and HCV medication combinations would be an impossible task.

Fortunately, several tools are available to aid clinicians in selecting HIV and HCV regimens that minimize DDIs. Dr Falade-Nwulia recommends consulting the user-friendly tables published in the AASLD/IDSA guidelines for the treatment of HCV infection. The tables can be found under the section, “Unique Populations: Patients with HIV/HCV Coinfection.”5 The tables are color coded to indicate which drug combinations are safe and which ones should be avoided because of DDIs.

Dr Chirch suggests additional resources, such as the HIV treatment guidelines issued by the US Department of Health and Human Services, which are updated at least once yearly and contain a section on drug-drug interactions.6 The AIDS Education & Training Center Program: Northeast/Caribbean has developed charts on DDIs for HIV medications as clinical support tools.7 In particular, Dr Chirch recommends the University of Liverpool’s HEP iChart website and mobile phone app, which may be used to identify DDIs between HIV ART agents and any other medication.8 “It’s really easy to use. I end up using this app very frequently,” she said. “If you plug in the medications that your patient is on and then plug in the medication that you want to use, it is difficult to miss any major problems.”

Important DDIs in HIV and HCV Treatment

Although resources are available to identify potential DDIs between HIV and HCV antiviral drugs, some general principles may help guide treatment selection. “The most recent iteration of the guidelines for the treatment of HIV recommend integrase inhibitor-based ART regimens as preferred regimens,” Dr Chirch said. DDIs are not as common with integrase inhibitors — which include dolutegravir, raltegravir, and elvitegravir — because they are metabolized by the uridine diphosphate glucuronosyltransferase pathway instead of by the CYP3A4 P450 system. However, Dr Chirch advised caution when using the integrase inhibitor elvitegravir because it requires boosting with cobicistat, which uses the CYP3A4 P450 enzyme, thus increasing the potential for DDIs.

According to Dr Chirch, some drug combinations should be avoided altogether. Protease inhibitors are widely used in the treatment of HCV and include grazoprevir, glecaprevir, and voxilaprevir. However, use of certain protease inhibitors for HCV with a boosted protease inhibitor for HIV that inhibits CYP3A4 P450 may elevate levels of the protease inhibitor for HCV, increasing the risk for liver toxicity in patients coinfected with HIV/HCV who already have some degree of liver disease. On the other hand, the ART agent efavirenz induces CYP3A4 P450, which may lead to lower levels of the co-administered drug, thereby potentially reducing its efficacy. “Efavirenz coadministration with most currently prescribed DAA regimens may be problematic, so that is one antiretroviral agent that you would consider switching off of if you were in that situation,” Dr Chirch said.

Tenofovir disoproxil fumarate (TDF), a nucleoside reverse transcriptase inhibitor commonly prescribed for HIV, is associated with renal toxicity. This risk may be further increased if TDF is used with some oral DAA therapies for HCV, according to Dr Falade-Nwulia. In particular, boosted protease inhibitor regimens may increase TDF exposure and raise the risk for renal toxicity. However, some combinations of TDF-based regimens plus oral DAAs for HCV present only a mild or moderate risk for renal toxicity, and therefore continuing treatment while closely monitoring kidney function may be an acceptable approach. A newer formulation of tenofovir, tenofovir alafenamide, is less nephrotoxic and has no DDIs with any of the oral DAA regimens for HCV.

Although no longer a preferred agent for HCV, ribavirin still sees use in combination with DAAs in patients who are treatment experienced or have liver cirrhosis. Using ribavirin-based regimens with some of the older nucleoside reverse transcriptase inhibitors — didanosine or zidovudine, for example — may lead to overlapping toxicities such as hepatic steatosis and lactic acidosis, and these combinations should be avoided, Dr Chirch said. Ribavirin can also cause dose-related hemolytic anemia, particularly when used with pegylated interferon. However, with newer agents available to treat HCV, anemia is now seen less frequently with ribavirin.

Managing DDIs in HIV/HCV Coinfection

The key principle to managing DDIs between HIV ART and HCV DAA therapy is to anticipate the problem before it occurs to prevent DDIs from happening, Dr Chirch said. In some cases, however, avoiding drug combinations that may lead to DDIs is not a feasible option. Some patients coinfected with HIV and HCV require a specific HCV regimen that is known to interact with their HIV regimen. If ribavirin must be used, for example, reducing the dose may help alleviate the risk for DDIs. The doses and dosing schedules of most other ART and DAA agents cannot be changed.

If the patient needs to be on a particular oral DAA regimen because of HCV genotype or severity of liver disease, their HIV ART treatment may need to be changed if the combination of regimens increases the risk for DDIs. “We are in a wonderful position now with so many options with ART that you can work with the patient to change their HIV regimen so that they are on a regimen that allows them to take an HCV oral DAA regimen,” Dr Falade-Nwulia said.

Before changing a patient’s HIV regimen, the clinician needs to ensure that the new regimen will maintain virologic suppression of HIV. Dr Chirch recommends obtaining a thorough history of prior ART regimens that have not worked for the patient and results of resistance testing to avoid using ART agents that may be ineffective and result in suboptimal outcomes.

Changing a patient’s HIV regimen also involves coordinated decision making with the patient. “You need to prepare the patient for the change,” Dr Falade-Nwulia said. “Sometimes [people with] HIV have been on their ART regimen for a really long time and they feel comfortable with this regimen.” Before starting HCV therapy, Dr Falade-Nwulia will switch the HIV regimen and monitor the patient for side effects and disease stability on the new regimen. She will then initiate HCV therapy once it becomes clear that the new HIV regimen is effective and the patient is comfortable with the treatment.

Modifying the HIV regimen to avoid DDIs with an HCV regimen is a complex and involved process. However, in a cohort study of 255 patients published in Hepatology, Dr Falade-Nwulia and colleagues found that only 30% of patients with HIV and HCV coinfection had to change their HIV regimens prior to starting DAAs for HCV.9 “Fortunately, the vast majority of patients with HIV/HCV coinfection do not require a switch in HIV therapy,” she said.

By Crystal Wong

References

  1. Scott JA, Chew KW. Treatment optimization for HIV/HCV co-infected patients. Ther Adv Infect Dis. 2017;4:18-36.
  2. Rice DP, Faragon JJ, Banks S, Chirch LM. HIV/HCV antiviral drug interactions in the era of direct-acting antivirals. J Clin Transl Hepatol. 2016;4:234-240.
  3. Qadir MI. Hepatitis in AIDS patients [published online: October 13, 2017]. Rev Med Virol. doi: 10.1002/rmv.1956
  4. Poizot-Martin I, Naqvi A, Obry-Roguet V, et al; Hepadat’AIDS Study Group. Potential for drug-drug interactions between antiretrovirals and HCV direct acting antivirals in a large cohort of HIV/HCV coinfected patients. PLoS One. 2015;10:e0141164.
  5. AASLD, IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Updated September 21,2017. Accessed November 28, 2017.
  6. US Department of Health and Human Services, AIDSinfo. Clinical Guidelines. Updated November 28, 2017. Accessed November 28, 2017.
  7. AETC Northeast/Caribbean. HCV drug interactions Guides—includes interactions with HIV and primary care medications. Updated 2017. Accessed November 28, 2017.
  8. University of Liverpool. HEP drug interaction checker. Reviewed November 28, 2017. Accessed November 28, 2017.
  9. Falade-Nwulia O, Sutcliffe C, Moon J, et al. High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center. Hepatology. 2017;66:1402-1412.
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Trump administration reportedly prohibiting several words from use in CDC budget documents, by other agencies http://www.eatg.org/news/trump-administration-reportedly-prohibiting-several-words-from-use-in-cdc-budget-documents-by-other-agencies/ Thu, 21 Dec 2017 04:40:23 +0000 http://www.eatg.org/?post_type=news&p=7119 Trump administration reportedly prohibiting several words from use in CDC budget documents, by other agencies; HHS, CDC officials offers statements; PEPFAR guidance document contains language shift

Washington Post: CDC gets list of forbidden words: Fetus, transgender, diversity
“The Trump administration is prohibiting officials at the nation’s top public health agency from using a list of seven words or phrases — including ‘fetus’ and ‘transgender’ — in official documents being prepared for next year’s budget. Policy analysts at the Centers for Disease Control and Prevention in Atlanta were told of the list of forbidden terms at a meeting Thursday with senior CDC officials who oversee the budget, according to an analyst who took part in the 90-minute briefing. The forbidden terms are ‘vulnerable,’ ‘entitlement,’ ‘diversity,’ ‘transgender,’ ‘fetus,’ ‘evidence-based,’ and ‘science-based’…” (Sun/Eilperin, 12/15).

Washington Post: Words banned at multiple HHS agencies include ‘diversity’ and ‘vulnerable’
“… A second HHS agency received similar guidance to avoid using ‘entitlement,’ ‘diversity,’ and ‘vulnerable,’ according to an official who took part in a briefing earlier in the week. … While HHS staffers were directly notified about how they must change the language they use when preparing budget documents, a shift is happening in other departments as well. At the State Department, for example, employees received a guidance document on Wednesday that outlined how they should develop country operating plans under the President’s Plan for Emergency AIDS Relief (PEPFAR) for 2018. This document repeatedly uses the phrase ‘sexual risk avoidance,’ which has been defined in recent congressional funding bills as abstinence-only practices until marriage, as the primary form of sex education. Jen Kates, vice president and director of global health and HIV policy at the Kaiser Family Foundation, said in an interview Saturday that while the document does not specifically change how much money should be spent on abstinence-only programs under PEPFAR, the heavy emphasis on it could shift priorities on how money is spent overseas. ‘It’s a change, and the language in these documents does matter, because that’s what’s communicated to the teams in the field,’ Kates said, adding that it’s ‘too early to tell’ how this might translate into funding changes…” (Sun/Eilperin, 12/16).

New York Times: Uproar Over Purported Ban at CDC of Words Like ‘Fetus’
“The Department of Health and Human Services tried to play down on Saturday a report that officials at the Centers for Disease Control and Prevention had been barred from using seven words or phrases, including ‘science-based,’ ‘fetus,’ ‘transgender,’ and ‘vulnerable,’ in agency budget documents. ‘The assertion that HHS has “banned words” is a complete mischaracterization of discussions regarding the budget formulation process,’ an agency spokesman, Matt Lloyd, said in an email. ‘HHS will continue to use the best scientific evidence available to improve the health of all Americans. HHS also strongly encourages the use of outcome and evidence data in program evaluations and budget decisions’…” (Kaplan/McNeil, 12/16).

STAT: CDC director tells staff ‘there are no banned words,’ while not refuting report
“…Dr. Brenda Fitzgerald, who has led the agency since July, sent an all-hands email to the agency’s staff assuring them that the CDC is committed to its mission as a science- and evidence-based institution. She later posted it on Twitter. ‘As part of our commitment to provide for the common defense of the country against health threats, science is and will remain the foundation of our work,’ Fitzgerald wrote. … Fitzgerald’s email to staff did not refute the Washington Post’s article reporting that CDC staff had been given a list of seven banned words by CDC budget analysts. … A Health and Human Services official who asked not to be named told STAT it was not accurate to say that CDC had been ordered not to use the seven words. Instead, he said, agency budget analysts were told that some words and phrasing might be more likely to win support for the CDC’s budget in the current Congress…” (Branswell, 12/17).

Additional reporting on this developing story is available from Al Jazeera, Associated Press, CNN, The Hill, PBS NewsHour, and TIME.

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Vitamin D found to be ineffective against ART-related lipid and metabolic dysfunction http://www.eatg.org/news/vitamin-d-found-to-be-ineffective-against-art-related-lipid-and-metabolic-dysfunction/ Thu, 21 Dec 2017 04:35:53 +0000 http://www.eatg.org/?post_type=news&p=7117 Vitamin D has been touted as a preventive treatment or therapy for multiple ailments, from brittle bones to cancer to autoimmune disorders. Several studies have suggested that individuals living with HIV who supplement their diets with vitamin D have a lower risk of developing Type 2 diabetes and elevated cholesterol levels, both of which are not uncommon in those with HIV who are being treated with antiretroviral therapy (ART). With this in mind, a team of scientists from the University of Alabama-Birmingham and other institutions set out to learn whether vitamin D had any positive effect on lipid levels and insulin resistance in HIV-positive individuals who were just beginning ART regimens.

The team enrolled 165 subjects in its double-blind study. The subjects were randomly assigned to either of 2 groups, one that received supplemental vitamin D and calcium and one that was given a placebo. The subjects’ vitamin D, glucose, insulin, and cholesterol levels, and BMI and waist circumference were measured at the beginning of the study (baseline), and at weeks 24 and 48 after ART had been initiated.

Both groups of subjects experienced significant increases in their cholesterol levels at week 24 and again at week 48, as well as moderate increases in their glucose levels over the course of the study. The placebo group saw insulin levels rise during the first 24 weeks while the vitamin D group did not, but neither group had statistically significant changes by week 48. Subjects in the placebo group experienced a slight increase in waist circumference as measured at weeks 24 and 48, but the increase was not statistically significant. Neither were the differences in BMI measured in the 2 groups.

“Despite the marked increase in vitamin D levels from the time of ART initiation and benefits regarding bone health, high-dose vitamin D and calcium supplementation did not meaningfully improve relevant metabolic parameters, including glucose metabolism, insulin resistance, lipid profiles, body composition measures, or prevalence of the metabolic syndrome,” the authors wrote in their study conclusions, adding, “Despite having low vitamin D levels throughout the study, participants in the placebo arm had only modest changes in the metabolic parameters measured.”

Why doesn’t vitamin D, given its beneficial effects on bone health, lower lipid levels and reduce insulin resistance in HIV-positive individuals who begin ART regimens? “It may be that metabolic changes related to ART initiation far outweigh the effects of vitamin D supplementation,” the authors wrote. “Alternatively, vitamin D supplementation may only be useful in persons who develop these metabolic derangements after some duration of exposure to the ART medications or that the [serum] level of [vitamin] D required to cause metabolic derangements is lower than that needed to maintain bone health.”

Limitations of this study include a short follow-up period (1 year), and the fact that the team used only 1 type of ART regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate on its subjects; a different medication regimen potentially could have changed the results. In addition, the subjects were young and otherwise healthy, which raises the question of whether vitamin D supplementation might have had a different impact on an already metabolically-impaired population. The exercise, alcohol, and smoking habits of the subjects were similarly unknown. In addition, women, who have been shown to be responsive to vitamin D supplementation in previous studies, were underrepresented in this trial.

By Laurie Saloman

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GNP+ survey: State of PLHIV around the world: back to basics http://www.eatg.org/news/gnp-survey-state-of-plhiv-around-the-world-back-to-basics/ Thu, 21 Dec 2017 03:37:47 +0000 http://www.eatg.org/?post_type=news&p=7111 People living with HIV around the world: GNP+ wants to hear from you!

The Global Network of People living with HIV (GNP+) is collecting input from people living with HIV (PLHIV) around the world to highlight the state of PLHIV and to shape the GNP+ strategic plan for 2018-2022.

You are invited to complete a survey available in English, Spanish, French and Russian here.

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New paper launched on hepatitis testing in community setting http://www.eatg.org/news/new-paper-launched-on-hepatitis-testing-in-community-setting/ Thu, 21 Dec 2017 03:35:15 +0000 http://www.eatg.org/?post_type=news&p=7100 Correlation Network announced the publication of a new paper on the importance of HCV testing in the Community! It includes background information, methods, good practices and much more.

Check out the paper here.

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MSF challenges Gilead’s patent application for hepatitis C combination treatment in China, to bring down prices http://www.eatg.org/news/msf-challenges-gileads-patent-application-for-hepatitis-c-combination-treatment-in-china-to-bring-down-prices/ Thu, 21 Dec 2017 03:32:21 +0000 http://www.eatg.org/?post_type=news&p=7108 Gilead recently launched one of these drugs for $100/pill in China

Geneva, 18 December 2017 – The international medical humanitarian organisation, Médecins Sans Frontières (MSF) has filed a legal patent challenge in China against US pharmaceutical corporation Gilead’s patent application for the combination of two crucial oral hepatitis C medicines, sofosbuvir and velpatasvir. This combination is the first direct-acting antiviral (DAA) treatment to be registered for use against all genotypes of the disease. Rejection of patents for this combination would pave the way towards the availability of affordable generic versions of this treatment that millions of people need in China and around the world.

The legal challenge, filed at the China State Intellectual Property Office (SIPO), offers technical grounds to show that the drug combination does not merit patenting under China’s Patents Law. If granted, the unjustified patent on the combination of these two medicines would give Gilead a monopoly over production and sale of the treatment in China. It would block Chinese generic companies from producing affordable versions, for use in China and globally.

“Despite the deadly toll the hepatitis C epidemic takes, pharmaceutical corporations like Gilead still have far too much control over who can access these lifesaving medicines, which is ultimately costing people their lives,” said Mickael Le Paih, Head of Mission for MSF in Cambodia. “In some high-burden countries where we work, hepatitis C treatment is not readily available due to high prices. Leveraging China’s ability to produce more affordable generics could significantly increase competition and bring prices down further, allowing many countries to get treatment to more people, faster.”

Globally, an estimated 71 million people have chronic hepatitis C infection and, without access to treatment, nearly 400,000 people die each year from its complications. With nearly nine million people infected, China has the highest prevalence of hepatitis C in the world. Yet access to these medicines that have proven to be a major breakthrough for the treatment of hepatitis C remains limited in China and many other middle-income countries due to exorbitant pricing.

In China, Gilead recently announced the market launch of sofosbuvir at a prohibitive price of US$8,937 per treatment course, or around $100 per pill. The price of the sofosbuvir and velpatasvir combination in China is still not known, as the treatment is not yet registered or available in the country; but using sofosbuvir at Gilead’s price, in combination with another DAA, daclatasvir, would cost about $12,000 for the 12-week treatment. Generic competition has driven the price of this same treatment combination to as low as $120 per 12-week treatment in countries where patent barriers do not exist.

“With this patent challenge, MSF hopes to prevent Gilead from getting unmerited patent rights on the combination of sofosbuvir and velpatasvir, which would allow them to charge unreasonably high prices,” said Yuanqiong Hu, Legal Advisor for MSF’s Access Campaign. “The world desperately needs more affordable sources of these essential hepatitis C medicines to save lives and contain this growing epidemic, and the best way to achieve this is to open the door widely to robust competition among generic producers.”

Gilead has applied for multiple patents in China for its hepatitis C medicines, and some of these are being opposed by other pharmaceutical companies and non-profit organisations based on similar grounds of being unmerited under China’s Patents Law. Since 2015, SIPO rejected two key patent applications for sofosbuvir in China. Gilead’s patent applications on sofosbuvir and its combinations have also been challenged in many other countries, including Brazil, India, Russia and the United States, as well as in the European Union. Some of the Gilead’s patent applications have been rejected in Argentina and Egypt.

MSF treats people with hepatitis C in 11 countries (Belarus, Ukraine, Pakistan, Uzbekistan, India, Myanmar, Cambodia, Uganda, Kenya, Mozambique and South Africa). Since 2015, MSF has provided DAA treatment to over 5,000 people with hepatitis C. Of those who have completed treatment to date, the overall cure rate – measured by ‘sustained viral response’ – is 94.9 per cent.

Information on currently available diagnostics and treatments for hepatitis C, including pricing and registration information from manufacturers of DAAs, can be found in MSF’s issue brief, Not Even Close.

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Kaiser Family Foundation updates fact sheet examining PEPFAR’s role, efforts http://www.eatg.org/news/kaiser-family-foundation-updates-fact-sheet-examining-pepfars-role-efforts-2/ Thu, 21 Dec 2017 03:30:31 +0000 http://www.eatg.org/?post_type=news&p=7105 Kaiser Family Foundation: The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR)

This updated fact sheet examines the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and its role in addressing global HIV/AIDS, including its structure, treatment and prevention targets, results, funding, and key issues.

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O’Neill Institute for National and Global Health Law at Georgetown University: Reorganization and the Future of PEPFAR: Implications of State And USAID Reform

Findings, issued in a report published by the O’Neill Institute for National and Global Health Law at Georgetown University, represent the first analysis from the global health community and experts in PEPFAR operations to examine proposals to reorganize the State Department and USAID.

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Stop TB and Global Fund deepen cooperation to find missing cases of TB http://www.eatg.org/news/stop-tb-and-global-fund-deepen-cooperation-to-find-missing-cases-of-tb/ Thu, 21 Dec 2017 03:25:13 +0000 http://www.eatg.org/?post_type=news&p=7104 GENEVA, 18 December 2017 – The Stop TB Partnership and the Global Fund today signed a new collaboration agreement to contribute towards the goal of finding and treating an additional 1.5 million people with tuberculosis who are currently missed by health systems.

Under the TB Strategic Initiative, the Stop TB Partnership will work with national TB programs and partners in 13 countries, providing technical support through a combination of innovative approaches and best practices to remove barriers to accessing TB services, with a particular focus on key populations and vulnerable groups.

In 2016, 10.4 million people got sick with TB, an entirely preventable and curable disease. Only 6.3 million were detected and officially notified, leaving a gap of 4.1 million people who were “missed” by health systems after failing to be diagnosed, treated or reported. The result is many will die or continue to be sick and transmit the disease or, if treated with improper drugs, contribute to the growing menace of drug resistance.

The agreement is part of the TB Catalytic Investment initiative, an ambitious effort that brings together WHO, the Stop TB Partnership, the Global Fund and other implementing partners to stop the spread of TB and reach the global goal of ending TB as an epidemic by 2030.

Lucica Ditiu, Executive Director of the Stop TB Partnership, said the agreement will provide much-needed impetus to help countries begin closing gaps by finding cases of both drug-susceptible TB and drug-resistant TB.

“We have set an ambitious target of finding and treating an additional 1.5 million missing cases of TB by 2019. This agreement allows us to work shoulder-to-shoulder with the Global Fund, implementers and health partners in ensuring we reach our objective,” Dr. Ditiu said.

“Missing TB cases including drug-resistant TB are major challenges in fighting the disease, and pose a serious threat to global health security,” said Marijke Wijnroks, Interim Executive Director of the Global Fund.

“Only through partnership and smart investments will we achieve the global goal of ending TB as an epidemic,” said Dr. Wijnroks.

The TB Catalytic Investment initiative includes US$115 million in matching funds designed to support country-led programs; a US$65 million multi-country TB investment for programs focused on migrant and cross-border issues, the mining sector, refugees, improved laboratory services, and transition to domestically funded health programs; and the US$10 million TB Strategic Initiative. The 13 countries that are part of the TB Catalytic Investment initiative are Bangladesh, Democratic Republic of Congo, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, South Africa, Tanzania, Ukraine, Kenya, Mozambique and India.

Some key interventions of the TB Strategic Initiative include carrying out gender and legal assessments to help remove barriers to accessing TB services, developing a handbook on best practices and innovative case-finding activities, and providing technical assistance to help countries implement Global Fund-supported interventions.

Deaths from drug-resistant TB – when tuberculosis bacteria do not respond to first-line TB drugs – now account for about one-third of all antimicrobial resistance deaths worldwide. The rise of antimicrobial resistance coincides with the growth of TB. Despite steady progress since 1990, the disease killed 1.7 million people in 2016 (including 400,000 HIV-positive people), surpassing HIV as the deadliest infectious disease globally.

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EMA to occupy temporary facility until new HQ is ready http://www.eatg.org/news/ema-to-occupy-temporary-facility-until-new-hq-is-ready/ Thu, 21 Dec 2017 03:19:57 +0000 http://www.eatg.org/?post_type=news&p=7110 The Europeans Medicines Agency, which is relocating to Amsterdam following Brexit, said its new headquarters will not be ready until November 2019 and until then will occupy space provided temporarily by the Dutch government.

Read the full story here.

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VBI Vaccines announces initiation of Phase 3 clinical program for Sci-B-Vac® hepatitis B vaccine http://www.eatg.org/news/vbi-vaccines-announces-initiation-of-phase-3-clinical-program-for-sci-b-vac-hepatitis-b-vaccine/ Thu, 21 Dec 2017 03:03:55 +0000 http://www.eatg.org/?post_type=news&p=7106 Patient dosing commenced on December 18, 2017
4,800 subjects across two Phase 3 studies: PROTECT and CONSTANT
15-month program – headline data expected Q2 2019

December 19, 2017: VBI Vaccines Inc. (Nasdaq: VBIV) (TSX: VBV) (“VBI”) announced today the initiation of the global Phase 3 clinical program for Sci-B-Vac®, its third-generation hepatitis B vaccine, with the commencement of patient dosing on December 18, 2017.

The Phase 3 program will be a global 15-month program consisting of two concurrent Phase 3 studies – a safety and immunogenicity study (PROTECT) and a lot-to-lot consistency study (CONSTANT), enrolling a total of approximately 4,800 subjects. The Phase 3 program will be conducted at approximately 40 sites across the U.S., Europe, and Canada.

Dr. Francisco Diaz-Mitoma, VBI’s Chief Medical Officer, commented, “The initiation of this Phase 3 program is a significant milestone for VBI. There is an extensive safety and efficacy data package that currently exists for Sci-B-Vac, with approximately 2,000 subjects in past clinical trials and over 500,000 subjects who have received the vaccine in the commercial setting. Pending data from this Phase 3 program, we expect to submit marketing authorization applications to U.S., European, and Canadian regulatory authorities in 2019. We believe there is a recognized need for an improved Hepatitis B vaccine and we are committed to advancing Sci-B-Vac through Phase 3 development as quickly as possible.”

Dr. Nathan Segall, a certified internal medicine, allergy, and immunology specialist at Clinical Research Atlanta and a Principal Investigator in the program, added, “Sci-B-Vac is the only commercially-available vaccine that contains the pre-S1 and pre-S2 surface antigens. The field is looking forward to seeing the results of this pivotal program, adding to the growing body of research which suggests that the inclusion of these two antigens may prove more immunogenic, especially in subjects that currently do not respond optimally to current standard of care.”

About PROTECT – Safety and Immunogenicity Study

PROTECT will be a double-blind, two-arm, randomized, controlled study. Approximately 1,600 adult subjects, 18 years of age and older, will be randomized in a 1:1 ratio to receive either a three-dose course of Sci-B-Vac 10μg or a three-dose course of the control vaccine, Engerix-B® 20μg. Enrollment will be stratified by age group.

The co-primary objectives of the study will be:

  • To demonstrate non-inferiority of the seroprotection rate induced by Sci-B-Vac vs. Engerix-B® four weeks after the third vaccination in adults age 18 and older.
  • To demonstrate superiority of the seroprotection rate induced by Sci-B-Vac vs. Engerix-B® four weeks after the third vaccination in adults older than 45 years of age.

The study will also include multiple secondary objectives to evaluate the speed to seroprotection, including assessment after two doses of Sci-B-Vac vs. three doses of Engerix-B®, and the overall safety and tolerability of Sci-B-Vac vs. Engerix-B®.

About CONSTANT – Lot-to-Lot Consistency Study

CONSTANT will be a double-blind, four-arm, randomized, controlled study. Approximately 3,200 adult subjects, age 18-45 years, will be randomized in a 1:1:1:1 ratio to receive one of four three-dose courses: Lot A of Sci-B-Vac 10μg, Lot B of Sci-B-Vac 10μg, Lot C of Sci-B-Vac 10μg, or the control vaccine Engerix-B® 20μg.

The primary objective of this study will be:

  • To demonstrate lot-to-lot consistency for immune response as measured by geometric mean concentration (GMC) of antibodies across three independent, consecutive lots of Sci-B-Vac four weeks after the third vaccination.

The secondary objective will be to evaluate safety and efficacy of Sci-B-Vac vs. Engerix-B®.

About Sci-B-Vac®

Sci-B-Vac® is a licensed third-generation hepatitis B vaccine that has demonstrated safety and efficacy in over 500,000 patients. Sci-B-Vac is currently approved for use in Israel and in 14 other countries. In contrast to second-generation hepatitis B vaccines, which contain only one surface antigen (the S antigen), Sci-B-Vac contains the S antigen and the pre-S1 and pre-S2 surface antigens. The composition of Sci-B-Vac may prove more immunogenic in subjects that currently do not respond optimally to second-generation vaccines.

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CATIE: December 2017 issue of TreatmentUpdate now online http://www.eatg.org/news/catie-december-2017-issue-of-treatmentupdate-now-online/ Thu, 21 Dec 2017 03:00:36 +0000 http://www.eatg.org/?post_type=news&p=7102 TreatmentUpdate is CATIE’s flagship digest on cutting-edge developments in HIV and hepatitis C research and treatment.

TreatmentUpdate 223: Inflammation and HIV, December 2017 issue is available at:

http://www.catie.ca/en/treatmentupdate/treatmentupdate-223

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The drug decimating Russia’s women http://www.eatg.org/news/the-drug-decimating-russias-women/ Thu, 21 Dec 2017 02:58:19 +0000 http://www.eatg.org/?post_type=news&p=7114 Designer drugs called ‘bath salts’ in the U.S. are dangerous to Americans, but addiction is epidemic among Russians, especially women. Many shoot up, and many contract HIV/AIDS.

Read the full story here.

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Collision of communicable and non-communicable disease epidemics—the case of HIV and COPD http://www.eatg.org/news/collision-of-communicable-and-non-communicable-disease-epidemics-the-case-of-hiv-and-copd/ Thu, 21 Dec 2017 02:55:45 +0000 http://www.eatg.org/?post_type=news&p=7112 In The Lancet Global Health, Jean Joel Bigna and colleagues report the results of their systematic review and meta-analysis of studies of chronic obstructive pulmonary disease (COPD) in people with HIV.

To read the full study, click here.

To read an accompanying comment, click here.

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Brazil’s AIDS fight falls victim to success http://www.eatg.org/news/brazils-aids-fight-falls-victim-to-success/ Thu, 21 Dec 2017 02:28:09 +0000 http://www.eatg.org/?post_type=news&p=7103 Complacency has created a new generation of victims.

From graft to homicide, Brazil these days has no dearth of homemade misery. Now a spike in illnesses inflicted by a deadly virus has unveiled yet another, crueler facet of Brazil’s woes: that it can be punished even for success.

Data from the public health ministry released early this month shows that AIDS — a scourge Brazil appeared on track to beat — is on the rise among some demographics (young men) and regions (the north and northeast). Yes, fatalities from the virus continue to retreat, and illness among young and elderly women has risen only slightly. (Because reporting HIV infections became compulsory only in 2014, the ministry bulletin did not report trends for new detections of the virus.)

Yet new AIDS cases are soaring among young males, with reported illnesses nearly tripling from 2006 to 2016 among teenage men aged 15 to 19, while doubling among young adult males aged 20 to 24.

Independent research conducted in Rio de Janeiro also indicated alarming rates of HIV infections among vulnerable and neglected groups, including 5 percent of female sex workers, 14 percent of men who have sex with men, and 6 percent of drug users.

While many developing countries — and most of Brazil’s continental neighbors — face far worse, the persistence of HIV and AIDS in Latin America’s biggest nation is troubling. Starting in the 1990s, Brazil led the fight against the epidemic, showing how a developing nation could treat the sick while also taking on drug companies and their legal eagles. Its efforts drew Big Pharma’s ire but accolades from world policymakers, inspiring developing countries ravaged by what was then still a poorly understood epidemic.

Rewriting the rules for fighting a frightening pandemic, Brazil made the once-contested universal preventive “test and treat” strategy a global best practice. “Today the World Health Organization and the United Nations endorse test and treat, a protocol the World Bank opposed 20 years ago,” Draurio Barreira, an epidemiologist at the World Health Organization who used to oversee Brazil’s HIV/AIDS program, told me.

Brazil demanded that drug companies sell cutting-edge retrovirals at deep discounts or risk seeing their patents breached in the name of national health. Officials in Brasilia even turned down a fat AIDS prevention grant because the United States Agency for International Development demanded that the country condemn prostitutes — a critical demographic in the national disease prevention strategy.

Brazil won the public relations battle by pioneering a program to give away cheap, generic antiretroviral drugs to AIDS victims. In 2014, the benefit was extended to anyone who tested positive for HIV. The offensive was a statement that public health was also politics, and that the campaign to contain HIV and AIDS was also a contest for hearts and minds.

As a result, the number of infections plummeted. So did the number of fatalities. Suddenly, HIV in Brazil was no longer a monster, but a manageable condition. And therein lay the peril.

Sure, plenty of factors contributed to HIV’s comeback, from increasing drug resistance by a wily virus to the rise in global travel, where every visitor is a potential vector. (Look no further than the 2015-16 Zika virus outbreak, triggered in part by international travelers.) But as health wonks have warned, a battlefield win against infectious disease can also numb authorities and the public into complacency.

First, the end of the emergency allowed people to lower their guards, just what pathogens like. Enter a new generation of sexually active teenagers and young adults, who grew up with the illusion that the worst was behind them, even as the digital age offered hook-up opportunities unforeseen by official safe-sex marketing strategies hatched a generation ago. “With universal access to health care, treatment at no cost, and plunging fatalities, many young people started to minimize HIV,” Adele Benzaken, who runs HIV and AIDS policy at the Brazilian health ministry, told me.

Brazil’s economic plight only worsened the condition, draining resources from public health and other social programs. Recently, the health ministry introduced an innovative therapy, known by its medical shorthand PrEP, designed to prevent HIV infection through a once-daily pill. But distribution is still incipient, limited to 7,000 targeted users to date.

One new obstacle to beating the contagion that lies beyond the bureaucrat’s brief is the rise of Christian evangelicals and social conservatives, who have mounted the bully pulpit just as the conversation over gender and sexual diversity has hit the media, campuses and the street. “The right wing is thwarting initiatives to raise awareness,” Mario Scheffer, a public health expert at the University of Sao Paulo told me. “It’s difficult to talk about sexuality and AIDS to young people with all the calls for censorship and pushback.”

Brazil sorely needs to reboot its strategy. Fortunately, health bureaucrats are quickly, if belatedly, overhauling their prevention protocols. They know that the traditional marketing strategies of pamphlets, television spots and condom giveaways at carnival have limited reach in the age of raves, Tinder and Snapchat.

Now the health ministry is preparing to blitz social media with slick safe-sex messages, and reintroduce campaigns for reproductive health in the classroom that had been suspended, after right-wingers howled that “sex education was the same as encouraging sex,” Benzaken said.

Brazil knows how to fight back. “We’ve never had so many tools to combat HIV and AIDS as we do today,” said Scheffer. All that’s needed now is to put these tools to use, quell the yahoos, and keep the country inoculated against the deadly scourge of complacency.

By Mac Margolis

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Should uninfected patients accept hepatitis C-infected livers to reduce waiting time? http://www.eatg.org/news/should-uninfected-patients-accept-hepatitis-c-infected-livers-to-reduce-waiting-time/ Wed, 20 Dec 2017 22:25:58 +0000 http://www.eatg.org/?post_type=news&p=7099 Study suggests that antiviral drugs may allow safe transplantation of HCV-positive livers into uninfected recipients.

A modeling study by Massachusetts General Hospital (MGH) investigators finds that the availability of directly-acting antiviral (DAA) drugs to treat hepatitis C virus (HCV) infection could allow the transplantation of livers from HCV-positive donors into HCV-negative recipients without posing undue risk. The team’s report will appear in the journal Hepatology and has been released online.

“The availability of donor livers continues to be the limiting factor in increasing the number of liver transplant surgeries,” says Jagpreet Chhatwal, PhD, of the MGH Institute for Technology Assessment, lead and corresponding author of the report. “Our study shows that transplanting HCV-positive livers into HCV-negative patients and treating with new antivirals can reduce waiting time to transplant and improve overall life expectancy.”

It is not uncommon for HCV-positive organs to be discarded and not utilized for transplant because of the risks associated with HCV infection after transplantation. The recent availability of DAA drugs to treat HCV-positive recipients has led to post-transplant cure rates greater than 90 percent, significantly improving overall transplant success. DAA drugs have also reduced the number of HCV-infected patients who progress to the point of requiring a transplant, increasing the proportion of patients needing a transplant for reasons other than HCV infection. At the same time, the persistent opioid epidemic has led to a greater number of potential donors infected with HCV, who are often young and otherwise healthy. All of these factors have led to increased interest in exploring the possibility of utilizing HCV-positive livers in HCV-negative patients on the transplant waiting list.

Since a randomized clinical trial of the use of HCV-infected donor livers in HCV-negative recipients would need to be large and conducted over several years, the MGH team decided to conduct a virtual trial by simulating the life courses of HCV-negative patients on the waiting list, and comparing probable outcomes under two scenarios – waiting for an HCV-negative liver or being open to accepting any appropriate liver, with the initiation of antiviral treatment if an HCV-positive liver was used. Based on the profiles of multiple patients on the liver transplant waiting list, the model included factors such as each patient’s probable waiting time, based on disease severity and geographic region; the supply of donor livers in each region, the risk of complications from an HCV-positive liver, and the efficacy of post-transplant antiviral treatment.

Their analysis revealed that the benefit of accepting an HCV-positive liver outweighs the risks in the majority of patients on the transplant waiting list. The magnitude of the benefits depended on the severity of a patient’s liver disease, which is measured by what is called a MELD score. Determined by a number of laboratory values, the MELD score ranges from 6 to 40, with a higher score indicating more severe illness. Patients can be referred for transplant evaluation with a score as low as 12, but the average MELD score for undergoing transplant is 28.

The MGH team found that HCV-negative patients with MELD scores of 20 or higher could benefit from receiving an HCV-positive liver, followed by antiviral treatment. The benefits were greatest for patients with scores of 28 and in regions hard hit by the opioid epidemic, such as the Northeast, that have greater numbers of HCV-positive donors.

“Prior to the availability of DAA drugs, the risks of transplanting HCV-positive livers into HCV-uninfected recipients were felt to be prohibitively high and not justifiable,” says Raymond Chung, MD, director of Hepatology, medical director of the MGH Liver Transplant Program and a co-author of the paper. “Every patient has extensive discussions with their care providers during the transplant listing process, part of which includes discussing the potential of accepting a ‘high-risk’ donor organ, such as one that tests positive for HCV. More clinical studies evaluating the use of HCV-positive donor livers and the efficacy and optimal treatment duration for antiviral drugs will be needed before this approach can be widely applied.”

Co-lead author Sumeyye Samur, PhD, of the MGH Institute for Technology Assessment says, “By simulating a virtual trial, we could assess the benefits and risks of transplanting HCV-positive organs into HCV-negative patients without putting patients at risk. Our study can thus inform efficient design of future trials and clinical practice in liver transplantation.”

Co-author Emily Bethea, MD, of MGH Gastroenterology and the Institute for Technology Assessment adds, “DAA treatment is expensive and is only covered by insurers for patients with documented HCV infection. If we hope to expand future coverage to HCV-negative patients on the transplant waiting list, we will need data on the cost-effectiveness of preemptive antiviral therapy to help payers recognize the importance and long-term success of this approach.”

Chhatwal stresses that, while the opioid epidemic has led to the increased availability of HCV-positive organs of all types, the trend should not be seen as beneficial. “The opioid epidemic is a major health crisis affecting communities across the country, and we want to reiterate our support for efforts to address the growing epidemic.”

Chhatwal is an assistant professor, Samur and Bethea are fellows, and Chung is an associate professor at Harvard Medical School. Additional co-authors of the Hepatology paper are Chin Hur, MD, MPH, MGH Institute for Technology Assessment; Turgay Ayer, PhD, Georgia Institute of Technology; Fasiha Kanwal, MD, MSHS, Baylor College of Medicine; Mark S. Roberts, MD, MPP, University of Pittsburgh School of Medicine; and Norah Terrault, MD, University of California San Francisco Medical Center. Support for the study includes American Cancer Society Research Scholar Grant RSG-17-022-01-CPPB, Health Resources and Services Administration contract 234-2005-37011C, National Institutes of Health grant DK078772, National Science Foundation award 1722665, and the MGH Research Scholars Program.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2017 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of “America’s Best Hospitals.”

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Using viruses to fight viruses: new approach eliminates ‘dormant’ HIV-infected cells http://www.eatg.org/news/using-viruses-to-fight-viruses-new-approach-eliminates-dormant-hiv-infected-cells/ Wed, 20 Dec 2017 22:19:10 +0000 http://www.eatg.org/?post_type=news&p=7098 While Ottawa researchers are known for their work on cancer-fighting viruses, one team is applying these viruses to a new target: HIV.

Researchers at The Ottawa Hospital and the University of Ottawa have discovered that the Maraba virus, or MG1, can target and destroy the kind of HIV-infected cells that standard antiretroviral therapies can’t reach. This laboratory discovery was published in the Journal of Infectious Diseases. If this technique works in humans, it might possibly contribute to a cure for HIV.

While daily medications keep the level of HIV virus in the blood low, there is currently no way to totally eliminate dormant HIV-infected cells from the body. If a person living with HIV stops taking antiretroviral medications, these hidden viruses rapidly rebound.

These latently HIV-infected cells are hard to target because they are not distinguishable from normal cells. Dr. Jonathan Angel and his team tried a new approach of identifying these dormant cells by using the MG1 virus. This virus attacks cancer cells that have defects in their interferon pathway, which makes the cells more vulnerable to viruses. Dr. Angel and his team previously found that latently HIV-infected cells also have defects in this pathway.

“We thought that because latently HIV-infected cells had similar characteristics to cancer cells, that the virus would enter and destroy them,” said Dr. Angel, senior scientist and infectious disease physician at The Ottawa Hospital, and professor at the University of Ottawa. “It turns out we were right.”

Using a number of laboratory models of latently HIV-infected cells, the researchers found that the MG1 virus targeted and eliminated the infected cells, and left healthy cells unharmed.

While most of these cells in patients are in the lymph nodes and other organs, a tiny number are found in the blood. When the researchers added MG1 to relevant blood cells taken from HIV-positive individuals, the levels of HIV DNA in the sample dropped. This indicated that the HIV-infected cells had been eliminated.

“We know that the Maraba virus is targeting and killing the latently HIV-infected cells, but we don’t know exactly how it’s doing this,” said Dr. Angel, who is also Head of the Division of Infectious Disease. “We think the virus is able to target the cells because of an impaired interferon pathway, but we need to do more research to know for sure.”

The research team’s next step is to try the virus in animal models of HIV or move directly to clinical trials pending funding and approvals.

All research at The Ottawa Hospital is supported by generous donors who contribute to hospital priorities, including research to improve patient care and a research chair in gay men’s health. The study was also funded by the Department of Medicine, University of Ottawa, Canadian Institutes of Health Research, Canadian Foundation for AIDS Research.

Full reference: “The oncolytic virus, MG1, targets and eliminates latently HIV-1-infected cells: implications for an HIV cure.” Nischal Ranganath, Teslin S. Sandstrom, Stephanie C. Burke Schinkel, Sandra C. Côté, Jonathan B. Angel. Journal of Infectious Disease. December 8, 2017.

The Ottawa Hospital: Inspired by research. Driven by compassion

The Ottawa Hospital is one of Canada’s largest learning and research hospitals with over 1,100 beds, approximately 12,000 staff and an annual budget of over $1.2 billion. Our focus on research and learning helps us develop new and innovative ways to treat patients and improve care. As a multi-campus hospital, affiliated with the University of Ottawa, we deliver specialized care to the Eastern Ontario region, but our techniques and research discoveries are adopted around the world. We engage the community at all levels to support our vision for better patient care. See www.ohri.ca for more information about research at The Ottawa Hospital.

University of Ottawa: —A crossroads of cultures and ideas

The University of Ottawa is home to over 50,000 students, faculty and staff, who live, work and study in both French and English. Our campus is a crossroads of cultures and ideas, where bold minds come together to inspire game-changing ideas. We are one of Canada’s top 10 research universities—our professors and researchers explore new approaches to today’s challenges. One of a handful of Canadian universities ranked among the top 200 in the world, we attract exceptional thinkers and welcome diverse perspectives from across the globe. www.uottawa.ca

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People with high viral load most likely to report sex that could pass on HIV http://www.eatg.org/news/people-with-high-viral-load-most-likely-to-report-sex-that-could-pass-on-hiv/ Wed, 20 Dec 2017 21:41:54 +0000 http://www.eatg.org/?post_type=news&p=7097 Half of those most likely to pass on HIV were not on treatment, despite guidelines

People with HIV who had high viral load were more likely to report vaginal or anal sex without a condom with a partner of unknown or different HIV status, a US study of people with detectable viral load has found.

Viral loads tended to be lower among those people with a detectable viral load who reported always using condoms, or who reported condomless sex only with other people with HIV.

The findings are published in the journal Sexually Transmitted Infections by a research team led by Dr Michael Stirratt of the Division of AIDS Research at the US National Institute of Mental Health.

The study looked at people who have a viral load above 1500 copies/ml. Research shows that undetectable viral load (below 50 copies/ml) eliminates the risk of HIV transmission; a large study in Uganda found no cases of HIV transmission from people with viral loads below 1500 copies/ml. Understanding sexual behaviour among people in HIV care with viral loads above 1500 copies/ml is therefore important if healthcare providers are to manage patients with a detectable viral load.

The researchers note that around one-third of people living with diagnosed HIV who were followed over a two-year period in a study of more than 250,000 people living with HIV in the United States had a detectable viral load above 1500 copies/ml. Furthermore, that study found that the period of detectable viral load above 1500 copies/ml lasted for an average of 316 days.

The researchers identified people with detectable viral load at six university-affiliated hospitals in the United States as part of an intervention study designed to improve control of viral load and to improve retention in HIV care. During the study, participants were asked to fill out an online interview about their sexual behaviour during the previous two months, with the assurance that the results would be completely anonymised and would not form part of their medical record.

Participants were asked if they had had anal or vaginal sex in the previous two months, and if they had had anal or vaginal sex without a condom. Participants who answered ‘yes’ had to specify whether condomless sex was with “someone you knew was HIV-positive” or “with someone who was HIV-negative or whose HIV status you didn’t know”.

The study enrolled 1315 people with viral loads above 1500 copies/ml, 61% of whom were taking antiretroviral treatment. The sample was 38% men who have sex with men, 32% heterosexual men and 30% women. Sixty-two per cent of the participants were black, 18% white, 18% Hispanic and 2% other.

Just over one-third of the sample reported anal or vaginal sex in the past two months (37%) and 60% reported that they always used a condom. Just under 30% reported that they only had condomless sex with other people living with HIV, and only 14% reported condomless sex with partners of unknown or different HIV status. This group comprised 68 people, of whom 43 had viral loads above 10,000 copies/ml. Twenty-one of those had viral loads above 50,000 copies/ml (very high).

Serosorting and condomless sex with partners of different or unknown HIV status were each reported more frequently by men who have sex with men, but the researchers found no difference in sexual risk behaviour according to whether the viral load was in the range of 1500 copies/ml to 10,000 copies/ml, or higher. Condomless sex with partners of different or unknown HIV status, and serosorting, were less common in people taking antiretroviral therapy, although this trend was not found to be statistically significant in a multivariate analysis which adjusted for factors such as race, risk category and viral load level.

The authors caution that they cannot estimate the viral load at the time of sexual activity, but they do know that all participants had a viral load measurement above 1500 copies/ml no more than four months prior to the interview, and 90% of samples tested were obtained no more than two months before the study interview.

They also note that because they did not interview people with viral loads below 1500 copies/ml – including those with undetectable viral loads – they cannot say to what extent their findings reflect wider patterns of sexual behaviour, especially among men who have sex with men. Nor do they know how many sexual partners their interviewees had, whether those of different HIV status were using pre-exposure prophylaxis (PrEP), or how frequently condomless sex took place with partners of different HIV status.

The authors emphasise that only a small proportion of people with detectable viral load reported sexual behaviour with the potential to transmit HIV, but these individuals tended to have especially high viral loads. The authors say that among those on treatment, poor medication adherence and over-reporting of medication adherence are the most likely explanations for high viral loads. Nevertheless, the study also found that 39% of all people who qualified for the study did so because they were not taking antiretroviral treatment at the time of the study (2014-2015) when treatment was already recommended for all US patients with HIV. Half of all people reporting condomless sex with partners of unknown or different HIV status were not taking antiretroviral therapy.

“Directing interventions to patients in care with high viral loads and concurrent sexual transmission risk behaviours could strengthen HIV prevention,” the authors conclude.

By Keith Alcorn

Reference

Stirratt MJ et al. Characterising HIV transmission risk among US patients with HIV in care: a cross-sectional study of sexual risk behaviour among individuals with viral load above 1500 copies/ml. Sex Transm Infect, published online first, 2 November 2017, doi:10.1136/sextrans-2017-053178

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Breastfeeding mediates pneumonia outcomes in HIV-exposed children http://www.eatg.org/news/breastfeeding-mediates-pneumonia-outcomes-in-hiv-exposed-children/ Wed, 20 Dec 2017 20:48:44 +0000 http://www.eatg.org/?post_type=news&p=7113 Investigators observed worse outcomes of pneumonia in HIV-exposed and uninfected (HIV-EU) compared with HIV-unexposed children, strongly mediated by breastfeeding, according to a report published in the Journal of the Pediatric Infectious Diseases Society.

HIV-EU children have a mortality rate twice that of unexposed children, as well as a higher incidence of pneumonia, and suffer worse outcomes. Between April 2012 and June 2016, a total of 352 children (245 unexposed; 107 HIV-EU) in Botswana were enrolled in a study to examine associations between HIV exposure and pneumonia outcomes in uninfected children.

The primary outcome of treatment failure after 48 hours occurred in 111 (32%) children, and 19 (5.4%) died. HIV-EU children were more likely to have treatment failure (relative risk, 1.57; 95% CI, 1.19-2.07; P =.002) and a higher in-hospital mortality rate (relative risk, 4.50; 95% CI, 1.86-10.85; P =.001) than unexposed children.

The sole candidate mediator that affected HIV exposure on the risk for treatment failure in unexposed children was low birth weight; accounting for 10% of the total effect. Current nonbreastfeeding was identified as a mediator of the effect of HIV exposure on the risk for in-hospital death, accounting for 47% of the total effect. Severe malnutrition, in utero exposure to antiretroviral therapy, and pneumonia severity were not significant mediators.

These results indicated more than a 4-fold higher risk for mortality for HIV-EU children and showed that nonbreastfeeding strongly mediated this effect, providing further evidence for a survival benefit of breastfeeding in HIV-exposed children. Results were limited by the exclusion of children with chronic medical conditions that predispose them to pneumonia, which may be another mechanism affecting outcome. However, investigators conclude that “adoption of current WHO recommendations for infant feeding by HIV-infected mothers would reduce pneumonia mortality rates among children.”

By Bradley van Paridon

Reference

Kelly MS, Zheng J, Boiditswe S, et al. Investigating mediators of the poor pneumonia outcomes of human immunodeficiency virus-exposed but uninfected children [published online November 20, 2017]. J Pediatric Infect Dis Soc. doi:10.1093/jpids/pix092

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EFGCP Conference Coming Up in February http://www.eatg.org/news/efgcp-conference-coming-up-in-february/ Mon, 18 Dec 2017 14:04:04 +0000 http://www.eatg.org/?post_type=news&p=7090 The upcoming conference of the European Forum for Good Clinical Practice holds its next conference in Brussels in February 2018. The conference will pay special attention to the consequences of more and deeper involvement of patients in clinical research. EATG has been working with EFGCP in several projects for many years. Several EATG members will also attend the conference as speakers and contributors. Join us there if you can.

Compliance, Complexity & Collaboration: Proposals for System Re-design to Master the Human Factor & Risk Management

20 & 21 February 2018

Renaissance Hotel, Brussels, Belgium

To register, click here

The EFGCP Annual Conference 2018 on Compliance, Complexity & Collaboration: Proposals for System Re-design to Master the Human Factor & Risk Management  will take place in Brussels on 20 & 21 February 2018.

EFGCP is dedicating the 2018 Annual Conference to the “Human Factor” in clinical research. The aim is to identify strategies with which to keep our research compliant and efficient.  Though we may compete with each other, our interests in furthering clinical development are held in common. We can all gain from collaboration.  Working in a corner is no longer pragmatic for any of us: mutually beneficial collaboration is the only way to succeed.

You can also follow EFGCP on Twitter for more updates: @efgcp

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