A short course of HIV pre-exposure prophylaxis (PrEP) taken before and after sexual activity appears to significantly reduce the risk of HIV infection among high-risk men who have sex with men (MSM), according to an interim analysis of data from a major clinical trial. The findings were deemed to be so convincing that the study -- known as ANRS IPERGAY and based in France -- will be unblinded and all participants offered tenofovir/emtricitabine (Truvada), according to an announcement posted Oct. 29 on the study's official website.
The unexpected announcement comes less than three years into the IPERGAY trial, a study that was slated to eventually enroll 1,900 volunteers in France and Canada but currently has approximately 400. The randomized, placebo-controlled, double-blinded trial was designed to assess the efficacy of a unique strategy involving "on-demand" PrEP specifically among MSM:
- Volunteers took two study tablets (which contained either tenofovir/emtricitabine or placebo) no less than two hours before and no more than 24 hours before engaging in sexual intercourse.
- Volunteers took another single study tablet every 24 hours during the period in which sexual activity was taking place.
- Volunteers took a final study tablet 24 hours following the last dose they took during the period in which sexual activity was taking place.
The data safety monitoring board (DSMB) for IPERGAY recently examined unblinded interim data and found "a very significant reduction in the risk of HIV infection in the on-demand PrEP group," according to the official announcement.
Although no specific numbers were provided, the announcement noted that the risk reduction was "much higher" than that found in the iPrEx study, one of the key clinical trials that led to U.S. Food and Drug Administration (FDA) approval of daily tenofovir/emtricitabine for PrEP in 2012. The iPrEx study found that high-risk transgender women and MSM had a 42% overall reduction in HIV acquisition risk while taking daily PrEP -- a reduction that increased to 92% when specifically looking at volunteers with drug levels that clearly indicated consistent PrEP use. A follow-up, open-label extension (OLE) study further discovered that zero HIV infections occurred among volunteers who took the drug at least four days per week.
The IPERGAY announcement dovetails with a similar announcement by British researchers on Oct. 16 regarding the PROUD study, which was altered after a DSMB analysis discovered a significant HIV risk reduction among MSM and transgender women who began taking PrEP immediately compared to volunteers who were randomized to wait 12 months before beginning PrEP.
"The IPERGAY and PROUD study results are extremely encouraging," said Robert Grant, M.D., M.P.H., the protocol chair of the iPrEx study, in an interview with TheBodyPRO.com. "They indicate that the effect of PrEP is robust, and that PrEP should be made available as soon as possible to people who ask for it and who need it."
However, Grant stopped well short of suggesting that the IPERGAY announcement heralded an immediate change in recommendations regarding how PrEP should be dosed.
"The details of their findings have not been made available," he said. "I think it's great that they're showing high levels of efficacy, but I need to know exactly how high, and were there any PrEP seroconversions that occurred, and under what circumstances did they occur. I think we need to know the details before embracing the notion that intending to take PrEP before and after sex is as robust as intending to take it daily."
That view was shared by Walt Senterfitt, Ph.D., an HIV prevention epidemiologist and research ethicist at the Los Angeles County Department of Public Health. "Because we do not have the actual data from the trial available yet, we can't yet really answer some important questions that are already being oversimplified in media discussion," he told TheBodyPRO.com. "For now, the messaging about PrEP use should not change, but we have another reason to be urgent in making it more widely available and continuing to closely follow real-world effectiveness in various populations, including women, trans folk and IDU [injection drug users]."
Full IPERGAY trial results "should be available" early next year, according to the official announcement on the study. In the meantime, as a result of the DSMB findings, the French National Agency for AIDS Research (ANRS) -- which sponsored IPERGAY -- elected to make tenofovir/emtricitabine available to all study participants immediately. The study itself will continue for at least an additional year "to ensure the continued long-term benefit of 'on-demand' PrEP and also assess its long-term safety," the announcement stated.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.