By Michael Smith
North American Correspondent, MedPage Today
Action Points: Efficacy maintained although condom use fell
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- On-demand pre-exposure prophylaxis (PrEP) against HIV among gay men at high risk remained highly effective even with a low rate of condom use in a randomized, placebo-controlled trial and an open-label extension.
DURBAN, South Africa — Low condom use did not undermine the efficacy of “on-demand” pre-exposure prophylaxis (PrEP) among gay men at high risk for HIV, a researcher said here.
In an open-label extension of the randomized placebo controlled IPERGAY trial, only one participant of more than 360 acquired HIV over a year and a half of follow-up, according to Jean-Michel Molina, MD, of the Saint-Louis Hospital in Paris.
The incidence of HIV was actually lower in the extension study than it had been in the randomized trial, even though the rate of condomless sex rose, Molina reported at the International AIDS Conference.
The IPERGAY study had 400 participants, randomly assigned to take an anti-HIV medication — the single-pill combination of tenofovir/emtricitabine (Truvada) — or a placebo before and after sexual encounters.
In IPERGAY and its extension, participants were instructed to take two tablets between two and 24 hours before having sex, another the following day, and a final pill the day after that. The process could continue with a pill a day if there were continuing sexual encounters.
The blinded part of the study was stopped early because the data showed an 86% relative reduction in the incidence of HIV among participants getting the active drug.
Molina said that, with the early halt, the study might have overestimated the benefit, since efficacy might have waned over a longer study period. But investigators had already planned for an open label extension and were able start it within a few days of unblinding the randomized trial.
The 335 participants remaining in IPERGAY at the time and 33 new patients were offered the drug; some 299 had completed follow-up on June 30, 2016, Molina said.
Data on those patients showed a single new infection — a man who had stopped PrEP because he was in a stable relationship with a man whom he mistakenly thought to be HIV-negative.
The cumulative probability of HIV acquisition in the placebo group was 6.6 per 100 person-years, Molina reported. It was 0.91 per 100 patient-years at the end of the blinded trial for those getting the active drug and fell to 0.19 per 100 patient-years at the end of the open label extension.
In the blinded part of the trial, Molina said, patients reported taking the medication correctly 42% of the time. In the extension study, that rose to 50%, a difference that was statistically significant.
The finding is paralleled by several other PrEP studies, in which adherence rose after clinical trial results assured patients that the intervention was effective.
Adherence as measured by tenofovir plasma levels was also higher in the extension phase, although the difference did not reach significance.
The rate of self-reported receptive anal sex without a condom was steady at about 70% during the blinded part of the study, but rose from 77% to 83% over the course of the extension — a trend that was statistically significant.
On the other hand, Molina reported, the rate of sexually transmitted infections was not significantly different between the two parts of the study.
The results are “not so much a surprise,” commented LaRon Nelson, PhD, RN, of the University of Rochester in New York state, who was not part of the study but who co-moderated the session at which it was presented.
“When people understand how they can manage their prevention, they customize strategies that work best for them,” he told MedPage Today.
“It’s different when you tell a patient you have to do this every day,” Nelson said. Instead of trying, he added, “they often say to themselves ‘I can’t do that’ and they ditch the whole thing.”
The flexibility of the on-demand approach “could make PrEP more acceptable,” he said.
The original blinded study showed that the PrEP was safe with roughly the same number of adverse events and serious adverse events in both arms, Molina said. In the extension, he said, “safety was similar and pretty good.”
The study had support from the French AIDS and hepatitis research agency, the Canadian HIV Trials Network, the Bill and Melinda Gates Foundation, the Pierre Berge Foundation, SIDACTION, and Gilead. Molina disclosed relationships with BMS, Merck, Gilead, Janssen, and ViiV. Nelson made no disclosures.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Primary Source: International AIDS Conference
Source Reference: Molina J-M, et al “Efficacy of “On Demand” PrEP in the ANRS IPERGAY Open-Label Extension Study” AIDS 2016.