People who took HIV pre-exposure prophylaxis (PrEP) "on demand" -- that is, before and after sex -- were just as likely to prevent HIV infection as people who took PrEP once a day, according to interim results of a study presented at the 22nd International AIDS Conference (AIDS 2018) on July 25. The findings are particularly important for men who have sex with men (MSM), who comprised nearly 99% of the people recruited for the study. Currently, the U.S. Food & Drug Administration (FDA) has only approved PrEP as a once-daily pill.
The interim data were presented by the study's lead author, Jean-Michel Molina, M.D., Ph.D., a professor of infectious diseases at University of Paris Diderot. (The study name, Prévenir, is French for "prevent.") Molina and colleagues enrolled participants and gave them the option of utilizing either the daily or the "on-demand" dosing method for PrEP, with the opportunity to change strategies at any time. The study ultimately aims to enroll 3,000 people in the Paris metropolitan region; these interim results included roughly 1,600 people. Approximately 55% of the participants chose the on-demand option.
At this point in the three-year observational trial stage (May 2017-May 2020), there have been no new HIV infections in either arm of the trial, Molina reported.
"That's remarkable," declared Molina. "[The study] shows that the incidence of HIV in this cohort is zero ... averting 85 new infections." The study also has so far yielded a very low rate of volunteers who were lost to follow up or who discontinued their participation, and the number of adverse events did not differ significantly between the two arms. Data on sexually transmitted infection acquisition was not presented; however, 20% of participants reported consistent condom use.
On-demand PrEP, also referred to as intermittent or pericoital PrEP, requires the user to take "2 pills of Truvada [tenofovir/emtricitabine] within 24 to 2 hours prior first sexual intercourse, then 1 pill every 24 hours during the period of sexual activity with one pill after the last sexual intercourse, and one last pill 24 hours later," according to the ClinicalTrials.gov listing for the Prévenir study.
The effectiveness of this regimen of PrEP dosing was previously demonstrated in the IPERGAY study, which was halted prematurely due to a clear, significant reduction in HIV incidence among men who have sex with men (MSM).
Even though it will be another two years before the full results of this study can be revealed, the interm results, along with prior research, have already had an impact on guidelines for PrEP. Several health bodies, including the French government, now support on-demand PrEP as a viable option for HIV prevention, and the International Antiviral Society-USA (IAS-USA) officially endorsed this regimen as an "alternative to daily PrEP for MSM with infrequent sexual exposures" in its newly updated antiretroviral guidelines. This endorsement may have a great impact on PrEP uptake and continued PrEP usage in the U.S., should the FDA and Centers for Disease Control and Prevention (CDC) also update their guidelines for prescribing PrEP.
"The evidence for on-demand dosing of PrEP among gay and bisexual men is strong, and includes randomized clinical trials and carefully monitored clinical practice," Robert M. Grant, M.D., a professor of medicine at the University of California at San Francisco and the chief investigator on iPrEX, one of the initial major clinical trials that showed PrEP to be efficacious at preventing HIV infections, said. "The new IAS-USA guideline is welcome, and will encourage a greater diversity of men to consider PrEP among the ways to enjoy sex and avoid infection."
Earlier this year, the CDC released data showing that only 3% of Latinx and 1% of black people in America who could potentially benefit from PrEP have actually been prescribed the drug. In addition, PrEP use among gay and bisexual men, cisgender women, and transgender men and women of color is low.
Recent studies have explored factors that would help women in the U.S. South and transgender women access PrEP. However, those studies were based on the current daily PrEP guidelines -- and some say there are other challenges to making PrEP more accessible than the dosing frequency, even for MSM. "We are still far from reaching the number of people who need to be on PrEP in order to have significant impact on the [HIV] epidemic among MSM," Molina said.
Other experts agree with Molina's sentiment. "That's great that there is support for PrEP on demand, but we will still need to advocate for the policy changes that improve overall access to PrEP services, especially for key populations [and] black gay communities throughout the United States, said Christopher Hucks-Ortiz, M.P.H., who chairs the Black Caucus of the HIV Prevention Trials Network (HPTN). "Unfortunately, too many in our community are either still unaware about the existence of PrEP, or unaware that it could a good option for them. Even still, this is great news for HIV prevention in the United States."