What kind of prevention do gay men need?
The one that has been talked about most keenly and which continues to generate a great deal of data is pre-exposure prophylaxis.
How do we stop the hyperepidemic in gay men?
As we have already reported, a number of presentations at the 19th International AIDS Conference explored the 'hyperepidemic' of HIV amongst men who have sex with men, and especially black MSM. A paper by Gregorio Millet in The Lancet showed that, at least in the USA, the extremely high incidence and prevalence of HIV in this group is not driven by higher levels of unsafe sex. Instead, a combination of existing very high prevalence, the ease with which HIV is transmitted during anal sex, and the fact that black men (and some other subpopulations of gay men) have sex within small and multiply-connected networks have created a situation in which HIV is hard to avoid.
Given this, what prevention methods would work in gay men? The one that has been talked about most keenly and which continued to generate a great deal of data and debate at Washington was pre-exposure prophylaxis (PrEP) - taking antiretrovirals (ARVs) to prevent, rather than treat, HIV.
Will PrEP work?
The subject was already being discussed before the main conference in the satellite 'preconference' on gay men, men who have sex with men and transgenders (GMTs, to use a newly-coined acronym) organised by the Global Forum for Men who have Sex with Men and HIV (MSMGF) the day before the main conference opened.
Bob Grant, Principal Investigator of iPrEx, the proof-of-concept study of PrEP in gay men, told the preconference that in his view it was misleading to quote the 42% efficacy observed as if this was the highest achievable in gay men. Drug level studies in iPrEx (and in the Partners PrEP study in different-status heterosexual couples) had shown that the reduction in the risk of HIV infection in people with detectable drug in their blood - implying adequate adherence levels - was in the order of 90-92%, and that in iPrEx, in the relatively few subjects at US sites, drug had been detectable in 94% of samples.
In addition, in iPrEx as a whole, adherence had correlated with risk: participants who had unprotected receptive anal sex had higher adherence to PrEP than ones who didn't and PrEP efficacy was somewhat higher in this group as a result (53%). For Grant, this showed that PrEP is likely to be used by those who need it most. He recommended that use of PrEP should be guided by the person's request to have it more than the physician's judgement that they need it, and that PrEP and other biomedical prevention interventions are likely to work better in a non-judgmental atmosphere where stigmatising language is avoided.
In the main conference, in a symposium that discussed papers published in a special issue of The Lancet that focused on men who have sex with men (MSM), Patrick Sullivan of Emory University, Atlanta presented a model of the likely reduction in HIV infections in men who have sex with men (MSM) in four different countries (Kenya, the US, Peru and India) using three different prevention programmes: one with an intensified emphasis on condom use as its primary ingredient, one focusing on earlier treatment for MSM with HIV, and one adding PrEP to existing prevention programmes.
The base model used assumed one of the following three scenarios:
· Uptake of PrEP in gay men needing it at rates ranging from 20% to 80% and also at various adherence rates, ranging from 50% to 90%;
· an increase, ranging from 20% to 80%, in the proportion of men taking ARVs with CD4 counts above 200 cells/mm3 or (in the USA) 350 cells/mm3 (these being the ART thresholds at the time the model was done);
· an increase in condom use over baseline from 10% to 40%.
His model found that PrEP, under these scenarios, would be slightly more effective than condom promotion in all countries other than India, though only by a couple of percentage points in terms of the proportion of HIV infections averted that would otherwise have happened. For instance this proportion would be about 23% with 40% PrEP uptake, and about 20% with a 20% increase in condom use.
In all countries but Kenya, the model suggested that earlier treatment would have less effect than the other two interventions. The reason condoms would be more effective in India is because usage rates in MSM in that country are, at least in studies, higher, so a percentage rise in condom use would involve a greater number of extra condoms being used and have a greater effect on the remaining HIV transmissions. Conversely, in a country like Kenya where people currently start ART later than elsewhere, the consequence of starting it early is greater.
Sullivan said his model predicted that, using the most realistic scenarios, 25% of infections could be averted over the next ten years in MSM using a combination of these methods. However this would happen only if the criminalisation of male/male sex, threats and violence against MSM, lack of understanding and training among healthcare workers, and barriers against implementation research were addressed.
In a poster session, Kate Mitchell of the London School of Hygiene and Tropical Medicine found that the effectiveness of PrEP would vary widely according to how carefully gay men were targeted for it, using India as an example.
India has had quite a segregated MSM population historically, with feminine, gay-identified ‘kothi’ men who take the receptive role in sex and non-gay-identified ‘panthis’ who take the insertive role tending to stay in their separate populations (this means panthis, who do not identify as gay, are harder to reach). A third identity as ‘double decker’ or ‘dupli’, i.e. versatile, has grown up amongst urbanised gay men more recently.
In her model a PrEP intervention targeted at kothis or duplis, in which the intervention was 42% effective and was taken up by 60% of targeted men, would prevent 25-30% of HIV infections, whereas if PrEP were targeted at panthis, or selectively used by them, the result would be only a 5%-10% reduction in HIV infections.
Lifelong healthcare for gay men
Scientifically demonstrated prevention methods will only produce actual falls in HIV incidence if they concur with what gay men really need and want in terms of taking control over their health. This is what Ken Mayer, Director of Fenway Health, the largest gay-specific sexual health centre in the USA, argued in the Lancet symposium and related article.
The structural and psychosocial drivers of ongoing HIV and STI transmission in gay men had to be addressed as well, he said: homophobia has health consequences. Echoing Hillary Clinton earlier in the week, who said that “We have to stop treating HIV as an emergency,” he said that in the post-ART era, programmes that had started by dealing with the emergency of AIDS had to transition into ones providing chronic care for gay men, probably for a lifetime.
Mayer spoke of evidence that external rejection and stigma often leads to an internal state of self-hatred and conflict about sexuality that can in turn lead to depression, substance use to combat the depression, and loss of control over sexual risks, either directly due to low self-esteem or indirectly due to disinhibition. On the other hand, he said, “Having supportive conversations with adults and role models may lead to successful maturation.”
Mayer quoted research from 2003 (Stall) that asked 2674 gay men in four US cities if they had ever experienced childhood sexual abuse, depression, substance use or intimate partner violence. It then related recent high-risk sex and HIV prevalence to whether they had experienced none, one, two, or more than two of these problems. HIV prevalence was 13% in those who had experienced none of the problems and 21%-27% in those who had experienced any, and there was a linear increase, from 7% to 23%, in the proportion of men who had had recent high-risk sex according to whether they had had zero, one, two or more than two problems.
Mayer highlighted health inequalities in gay men, including greater biological vulnerability to sexually transmitted diseases. Amongst these are ones such as hepatitis A and B and HPV, that have effective vaccinations against them, which should be standard of care. He included ones not always thought of as sexually-related infections such as cytomegalovirus (CMV) and community-acquired MRSA.
Gay men also have twice the lifetime rate of depression as heterosexual men (40%), a 20% lifetime incidence of anxiety disorders, and higher rates of smoking and recreational drug use (though not injecting drug use or alcohol problems).
Civil rights for gay men could improve health outcomes directly, he said. He cited research from the state of Oregon (Hatzenbuehler 2011) which showed that suicides in gay teens were lower in Oregon counties that had gay/straight school student alliances, and that the medical and mental health costs at Fenway Health went down after the local state, Massachusetts, adopted gay marriage (Hatzenbuehler 2012).
However Mayer noted that HIV and STI rates continue to rise unabated in the US and Europe and asked if this was due to a time lag, to post-ART optimism, or to mis-tuned prevention messages. More data was needed on the link between structural change and HIV incidence in gay men, he said.
The important of gay-friendly healthcare workers
A crucial component of HIV/STI care and prevention for MSM was the support of a knowledgeable healthcare worker. “Healthcare providers may be uniquely able to assist MSM in their coming out process because of their social role,” Mayer said, and yet, ironically, gay men were often reluctant to come out because of fear of stigmatisation and received suboptimal care and outright prejudice when they did. “Culturally-competent healthcare is a basic human right, and is essential for optimal clinical management,” said Mayer.
Establishing a supportive healthcare environment was even more crucial in lower-income countries and ones where homosexuality was criminalised or gay men victimised, said Paul Semugoma, an openly-gay Ugandan doctor who works in private practice in Kampala.
He gave a powerful plenary speech in which he said that the denial and lack of recognition of male/male sexual behaviour in the country was promulgating dangerous myths, such as the idea that it is women who are spreading HIV to men and that anal sex is actually safer than vaginal sex (a belief confirmed by a study from Malawi (Wirtz), which found that 60% of a group of MSM in a community survey thought that vaginal sex was riskier than anal sex).
“You are not aware that MSM come and sit with you in the consulting room,” he told his fellow doctors. “You do not see them because if a man takes and HIV test surrounded by his workmates, he is not going to say ‘yes’ when asked if he has sex with men. Yet if you don’t know you are blind; you are not actually doing HIV prevention.”
This applies even more strongly to gay men with HIV, where there can be a mismatch between the sexual health strategies gay men feel they can use and the ones health providers think they have to give. A study (Caceres) of 840 people living with HIV in Peru, including 332 gay men, found that 60% of gay men in the more liberal and educated capital city, Lima, had a partner, compared with 30% in other cities, and that 32% of these were known serodiscordant relationships. Only 10% of men in Lima but 40% of men in other cities had had unprotected sex with their steady partner in the last month.
About a third of gay men relied on always using condoms as their main strategy to reduce the risk of HIV transmission to other partners, but others used a variety of other strategies. These included always disclosing (28%): avoiding anal sex (16%); sticking solely to mutual masturbation (17%) or oral sex without ejaculation (12%). A quarter of the MSM only had unprotected anal sex if they had an undetectable viral load.
This contrasted with the sexual advice they had received from healthcare workers. In 29% of cases, healthcare workers had recommended abstinence as the best safer sex strategy to; 92% had said ‘always use condoms’ and 75% had recommended only having one partner.
Participants commented that it was not the advice healthcare workers gave that was problematic, but the tone in which it was given. “They made me feel bad, the psychologist who gave the advice,” said one young gay man from outside Lima. “She said ‘you will have to limit yourself now, because you will not have any new relationships’.”
What MSM think of PrEP
In the MSMGF preconference, community advocates from several parts of the world presented the results of consultations with community members about PrEP. Brian Kanyemba of the Desmond Tutu Foundation in South Africa interviewed 67 community members and found that potential users were concerned about how long they might be on PrEP, how often they would have to test for HIV, how long they would have to wait after a negative test before receiving PrEP in order to avoid resistance, and who was going to pay for it.
“We can’t pay for it because most of us don’t have jobs,” said one, though there was disagreement over whether NGOs, the government, health insurance of pharmaceutical companies should pay for PrEP.
In Asia, Midnight Poonkasetwatana, Executive Director of the Asia Pacific Coalition on Male Sexual Health, said that community consultation had mainly turned up concerns about the practicalities of PrEP: would it have side effects? Would it disrupt sleep or diet? Would it reduce people’s resolve to use condoms? And would taking PrEP be seen by partners as equivalent to an HIV diagnosis, or be itself a mark of stigma, showing that the person tasking it was promiscuous or not to be trusted? Ironically, similar concerns were raised about the carrying of condoms in the past.
Matthew Rose of the Young Black Gay Men’s Leadership Initiative in the US said uncertainly about whether people could take it every day, the health implications of long term use, and whether longer-lasting or alternative drugs could be used, were among questions asked by his community members. One interesting question was whether, if gay men took PrEP in their 20s and did not use condoms, would they be de-skilled in condom use if they stopped taking PrEP in later life?
Finally, rectal microbicide researcher Ian McGowan on the University of Pittsburgh told the MSMGF preconference about future developments in PrEP and rectal microbicide research.
Would intermittent PrEP work better? This is the question addressed by the French IPERGAY study, which has been reported elsewhere, and which was presented by Principal Investigator Bruno Spire at the MSMGF preconference (the pace of PrEP approval is such that IPERGAY is now going to conduct a community consultation [press release in French] to see whether to retain the placebo arm in this study: a decision is due in the autumn.)
Answering the same question in a different way, with drug level monitoring, would be HPTN 066, which would compare drug levels in people who took Truvada daily against levels in people who took it twice weekly, once a week or who took a double dose twice weekly.
HPTN 067, also called the ADAPT study, would give 180 gay men in Bangkok and 180 heterosexual women in Cape Town intermittent PrEP: participants would be randomised 50/50 into ones taking PrEP twice-weekly, with a ‘booster’ PEP (post-exposure) dose if sex happened, or ones only taking it if sex was anticipated (also with a PEP dose if sex happened).
HPTN069 would be a year-long placebo-controlled study in US gay men in which Truvada (tenofovir/FTC) would be compared against the entry inhibitor drug maraviroc (Celsentri/Selzentry) used by itself, or maraviroc/tenofovir, or maraviroc/FTC.
In terms of rectal microbicides, having completed safety studies, a larger phase II study of a tenofovir-gel rectal microbicides, MTN-017, will probably start in the autumn of 2012. If this, a dosing and practicality study, produced a positive result, a phase 2b efficacy study was planned for 2014-2106 and we could have a rectal microbicide available by 2017 if it did prove effective.
The multiple challenges of HIV prevention in MSM
Darrell Wheeler, Dean of Loyola University in Chicago, spoke after McGowan and Spire at the MSMGF preconference. Mentioning the very high HIV incidence rates seen in black gay men in the USA , he said that doing HIV prevention in such a population involved addressing numerous challenges:
· the way unrecognised or stigmatised gay populations met each other and often only socialised in a small group;
· violence within intimate relationships;
· mental health and substance use;
· the legacy of sexual, physical and emotional violence;
· fatalism about HIV infection;
· and the internalised homophobia and stigma that could lead a person to conclude that they had a “flawed personal character”.
Against this, he said, “scaling up promising clinical interventions to community sustainable interventions” was a challenge, but it could be done.
By Gus Cairns
For all slides and webcasts presented in the Lancet special session on men who have sex with men and HIV, see http://pag.aids2012.org/session.aspx?s=650
For the MSMGF preconference programme, see http://www.msmgf.org/files/msmgf//documents/MSMGF2012Program.pdf
Millett G et al. Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis. Lancet 380(9839):341 – 348. 2012.
Sullivan PS et al. Successes and challenges of HIV prevention in men who have sex with men. Lancet 380(9839):388-399. 2012.
Mitchell KM et al. Sexual mixing patterns between men who have sex with men in southern India: implications for modelling the HIV epidemic and predicting the impact of targeted oral pre-exposure prophylaxis. Nineteenth international AIDS conference, Washington DC. Abstract THPDC0101.2012. See here for abstract.
Mayer KH et al. Comprehensive clinical care for men who have sex with men: an integrated approach. The Lancet 380(9839): 378 – 387. 2012.
Stall R et al. Association of Co-Occurring Psychosocial Health Problems and Increased Vulnerability to HIV/AIDS Among Urban Men Who Have Sex With Men. Am J Public Health. 2003 June; 93(6): 939–942.
Hatzenbuehler ML et al. The social environment and suicide attempts in lesbian, gay, and bisexual youth. Pediatrics 127(5):896-903. 2011.
Hatzenbuehler ML et al. Effect of same-sex marriage laws on health care use and expenditures in sexual minority men: a quasi-natural experiment. American Journal of Public Health 102(2):285-291. 2012.
Wirtz A et al. HIV prevalence, sexual risks and HIV knowledge among men who have sex with men (MSM) in Malawi: understanding risks among a stigmatized population and opportunities for interventions. Nineteenth international AIDS conference, Washington DC. Abstract FRLBX03.2012. See here for abstract and here for slides.
Caceres CF et al (presenter Cecarelli MA). HIV-positive gay and bisexual men in Peru: sexuality, disclosure and the disconnect between sexual health needs and access. Nineteenth international AIDS conference, Washington DC. Abstract THAD0501.2012. See here for abstract and here for slides.