Today at the Conference on Retroviruses and Opportunistic Infections (CROI), the French national HIV research agency ANRS announced results of the IPERGAY trial, which examined a novel dosing strategy for pre-exposure prophylaxis, or PrEP, among men who have sex with men (MSM). The study evaluated a three-day PrEP regimen of tenofovir plus emtricitabine (brand name Truvada) designed to be taken orally before and after sex. The researchers reported that PrEP reduced HIV risk among the MSM who were prescribed this regimen by an average of 86 percent.
Also today at CROI, researchers from the U.K. Medical Research Council presented the results of the PROUD open-label study, which found that daily oral PrEP using Truvada reduced risk among MSM in that study by 86 percent. These findings together provide encouraging additional evidence of the power of PrEP to reduce the risk of HIV infection.
PROUD adds to the substantial evidence regarding the efficacy of daily oral PrEP. The IPERGAY results provide the first evidence that an event-driven regimen was effective among high-risk MSM with frequent sex (median of ten sex acts per month and eight partners every two months). CDC cautions, however, that researchers do not yet know if this regimen will work among MSM who have sex less frequently or among other populations at high risk for HIV infection. In this study overall, available data suggest that men were taking PrEP an average of three to four days per week.
CDC continues to recommend daily dosing of PrEP and urges people at substantial risk for HIV infection and their health care providers to continue to follow current CDC guidelines.
IPERGAY was a randomized, placebo-controlled study that began in February 2012 and was stopped by an independent data safety review board in October 2014 because of high efficacy. At that point, 400 participants had been enrolled. Instead of a daily pill, as in previous PrEP studies, participants in the IPERGAY study were instructed to take pills three days around the time of sex. This included:
- A dose of two pills between 2-24 hours before having sex (or one pill, if the most recent dose was taken between 1 and 6 days ago)
- Two additional single-pill doses 24 and 48 hours after the last pre-sex dose
- Continue one pill daily if additional sex events took place before the above regimen was completed
Therefore, the number of days PrEP was taken each week would vary depending on the frequency of sex, sometimes resulting in near daily use. In any week where sex occurred, there could be as few as four PrEP pills used (with a single act of sex) or as many as eight (with daily sex).
Statement by Dr. Jonathan Mermin, M.D., M.P.H., Director, CDC National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention
"CDC welcomes the findings presented today by the IPERGAY and PROUD teams, which provide additional evidence of the power of PrEP to reduce the risk of HIV infection.
The IPERGAY trial provides the first evidence that an event-driven regimen is effective among high-risk MSM with frequent sex.
Since available data suggest that men in this study were taking PrEP an average of three to four days per week, CDC cautions that researchers do not yet know if this regimen will work among MSM who have sex less frequently and would therefore be taking PrEP less often.
It is not known whether the regimen will work if taken only a few hours or days before sex, without any buildup of the drug from prior use. Studies suggest that it may take days, depending on the type of sexual exposure, for the active drug in PrEP to build up to an optimal level for preventing HIV infection.
There are also no data on how effective this regimen would be for heterosexual men and women and injection drug users or on adherence to this relatively complex PrEP regimen outside a trial setting. CDC continues to recommend only daily use of PrEP, as approved by the FDA. IPERGAY findings combined with other recent research suggests that even with less than perfect daily adherence, PrEP may still offer substantial protection if taken consistently.
We applaud ongoing efforts like IPERGAY to identify PrEP dosing strategies that may be more acceptable than oral daily dosing for some individuals at risk, and could potentially lower costs. In addition, researchers are working to identify alternative delivery vehicles, including injectable PrEP and insertable products such as a vaginal ring. These are exciting avenues for research.
We encourage people at substantial risk for HIV infection to take steps to reduce their risk, including speaking with their doctor about PrEP. Daily, oral PrEP is recommended by CDC as an option for men who have sex with men, heterosexual men and women, and injection drug users."