It turns out that you can trust gay men at high risk for HIV to take care of their health -- even if they have to remember to take an HIV prevention pill before sex, even if they are using drugs to propel their sexual experiences.
That's the core of the findings of two studies presented at the International AIDS Society conference in Paris this year.
"These results should reassure people," said Jean-Michel Molina, M.D., Ph.D., principal investigator of the IPERGAY study, from which both results were drawn. "Are people who are having less frequent sex also protected by an on-demand approach? Indeed, that's the case. ... For people who use chemsex, is on-demand PrEP [pre-exposure prophylaxis] an option? People who take drugs for sex take PrEP quite well."
The key, he said, is that the protocol for on-demand PrEP can't just be a prescription for a pill. It has to also include counseling to talk to people about the risks they're willing to take. Molina, who runs a PrEP clinic in Paris, said that, in addition to writing a prescription for on-demand PrEP and instructing patients to take two pills (comprising tenofovir/emtricitabine, or Truvada) two hours before sex, one no more than 24 hours after and then another one 24 hours after that, he talks to them about how they think about the risks they're taking. Sometimes, he said, they'll want to use only PrEP as protection. Sometimes, they'll want to use only a condom -- though he said that in this group of people, condom use is already low and unlikely to get higher with physician counseling. Sometimes, they'll use both, he said.
"You have to work closely with your community," he said.
New Results, High Adherence
The new data builds on IPERGAY results released for the first time in 2014 and then in detail in 2015. In IPERGAY, 414 gay and bisexual men in France and Canada were randomized to receive either tenofovir/emtricitabine or a placebo and instructed in the on-demand protocol --two before sex, two after, staggered over 48 hours. Topline results presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2015 showed that use of on-demand PrEP reduced HIV transmissions by 86% compared with the placebo. The data suggested that, for every 18 men who used PrEP on demand, one new HIV transmission was averted. In the open-label extension, that effectiveness increased to 97%.
But, among that group of men who have sex with men (MSM) were specific subsets: men who, for instance, were having an average of one sexual encounter a week, compared with a median of 10 encounters a month. And then there were the men who continued onto the open-label extension of the study who reported using psychoactive drugs just before sex and having a higher likelihood of high-risk sexual behavior, such as being the receptive partner in sex and having so-called hardcore practices and more casual sexual partners.
So, researchers wanted to know whether this on-demand approach worked for those subsets, too.
In the chemsex study, researchers, led by Perrine Roux, looked at the 96 men who reported drug use before sex and the approximately 28 men who reported "slamming" -- that is, injecting drugs just before sex. They looked at sociodemographics between the chemsex and non-chemsex reporting group, as well as reported risk behaviors and the men's own perceptions of their risk.
They found that men who engaged in chemsex were demographically similar to men who didn't report chemsex, and both groups engaged in higher-risk sexual behaviors and knew they were engaging in higher-risk sex. Relatedly, the men who reported chemsex in their most recent encounter were more likely to have used PrEP and less likely to have used condoms. Even after adjusting for confounding factors, men who reported chemsex were 2.18 times as likely to report on-demand PrEP use as others in the study.
This is one of the great things about the study, said Molina: Because PrEP is for people at high risk for HIV, it allows researchers and providers to better understand the motivations and behaviors of these men, who have in the past been unlikely to reveal their real sexual behavior to their providers.
"I have a colleague from Australia who is visiting now, and he tells me he worries about on-demand PrEP," Molina said. "But with IPERGAY, we have published the best results for PrEP (efficacy) ever. That doesn't mean that people should take PrEP on-demand all the time, but it gives them more flexibility."
Less-Frequent Dosing Study
It's a critical question, said Guimette Antoni, the study statistician, who presented the data at IAS 2017 on people who had less-frequent sex.
"Some users were having sex so frequently that they were using daily or nearly daily PrEP," she said of the original trial. "That's why we were very frequently asked about the efficacy of on-demand PrEP among participants who had infrequent sexual intercourse and therefore used fewer pills."
So, Antoni and her team sorted participants based on the median number of pills they took a month and focused on the participants who used 15 or fewer pills a month, indicating sex about once a week. In that group, six people acquired HIV.
But all six of those men were in the placebo arm.
That means, said Antoni at AIS, that "the reduction of relative incidence ratio was 100% and significant."
The results drew laudatory comments from other presenters, with Sheena McCormack, M.B.B.S., M.Sc., FRCP, an investigator of the PROUD PrEP study, exclaiming, "Can I just say, 'Bravo?' That's brilliant!" And Bob Grant, M.D., M.P.H., protocol chair of the seminal iPrEx study, said that the results "address the major questions people have had about IPERGAY."
Limitations and Outstanding Questions
But the study results did raise a few questions. For instance, IPERGAY was conducted with only cisgender MSM, so no conclusions can be drawn on whether on-demand PrEP is effective in transgender men having "front hole" sex or cisgender women. More studies are needed on that, Molina told TheBodyPRO.com.
What's more, the men in the less-frequent-sex substudy were not, strictly speaking, having sex once a week. Instead, this was an analysis of men during periods when sex was less frequent. Sometimes they'd have, for lack of a better phrase, a dry spell. And then, they might have sex frequently for a week or a month or two. This led Gus Cairns of Aidsmap to wonder, "Is this about drug levels?"
"Was this, some people had enough PrEP left in their system to work from the last time?" he asked. "Or, are we also seeing people who clearly did not have it in their systems, or started using PrEP the moment they started to have sex again?"
The answer, Cecile Tremblay, M.D., of IPERGAY told Cairns and the audience, was that, "[w]hether sex was once a week or once a month, no matter what, there were zero new infections" among people in the PrEP arm." "And that's the limit of what we can say."