AT AIDS 2016
DURBAN, SOUTH AFRICA (FRONTLINE MEDICAL NEWS) – On-demand preexposure prophylaxis using oral antiretroviral therapy taken by men as little as 2 hours before engaging in high-risk sex with other men proved even more effective in preventing HIV transmission in the IPERGAY open-label extension study than in the original randomized, double-blind, placebo-controlled IPERGAY trial, Jean-Michel Molina, MD, reported at the 21st International AIDS Conference.
In the previously reported landmark double-blind IPERGAY trial, the incidence of HIV infection was 0.91%/year with tenofovir/emtricitabine (Truvada) for preexposure prophylaxis (PrEP) during 219 person-years of follow-up and 6.6%/year with placebo during 212 person-years of follow-up, for an 86% relative risk reduction ( N Engl J Med. 2015 Dec 3;373:2237-46 ). In the 299 participants in the open-label extension of IPERGAY, HIV infection occurred at a rate of just 0.19%/year during 515 person-years of prospective follow-up, translating to a 97% reduction in risk, compared with the placebo-treated controls in the parent study.
Moreover, the one patient who became HIV positive in the open-label extension study hadn’t used PrEP for months beforehand because he’d been in a stable relationship with a single partner, who turned out to be HIV infected, according to Dr. Molina, professor of infectious diseases at the University of Paris-Diderot and head of the infectious diseases department at Saint-Louis Hospital.
The rationale for on-demand, as-needed PrEP is that patients find it less burdensome than chronic daily therapy. The IPERGAY regimen entails taking a loading dose of two tablets of Truvada, each containing a fixed dose of 300 mg of tenofovir and 200 mg of emtricitabine, with food 2-24 hours before sex, followed by a third tablet 24 hours after the loading dose and a fourth tablet 24 hours after that. If a patient has multiple consecutive sexual episodes, he is to take one tablet per day until the last episode, then take the two postexposure tablets at 24-hour intervals.
Participants in the open-label extension study engaged in high-risk sex. At baseline they had averaged seven different sexual partners in the previous 2 months and engaged in condomless anal sex with at least two different partners in the prior 6 months.
At baseline 77% of subjects indicated their last experience of receptive anal intercourse was condomless. And even though all study participants received risk reduction counseling and free condoms, at the study’s end 86% of subjects said they were condomless for their most recent experience of receptive anal intercourse, a significant increase, compared with baseline.
The rate of non-HIV sexually transmitted infections was disturbingly high in both the open-label extension study and parent randomized trial. This will need to be addressed in future prevention studies, Dr. Molina said. During the open-label study, for example, 34% of men developed one or more chlamydia infections, 32% had gonorrhea, 19% syphilis, and 1% became infected with hepatitis C virus.
Patient questionnaire responses indicated 50% of subjects in the open-label study used PrEP correctly, a significantly better adherence rate than the 42% seen in the earlier double-blind study. Adherence is often better in open-label studies because participants are counseled that the regimen has been shown to be effective and there’s no chance they’ll receive a placebo. But the 24% rate of suboptimal PrEP use and 26% rate of no PrEP at last sexual intercourse in the extension study leave ample room for improvement, the researcher noted.
Adverse events in the open-label extension study were similar to those seen in the double-blind trial. Nausea/vomiting and other gastrointestinal symptoms were the most common adverse events, affecting 13% of subjects in the open-label study. All three study dropouts because of adverse events resulted from a drop in plasma creatinine clearance.
The IPERGAY studies were funded by the French National Agency for Research on AIDS and Viral Hepatitis. Dr. Molina reported serving as an advisor to Gilead Sciences, which markets Truvada, as well as a handful of other pharmaceutical companies.