Can PrEP on Demand for HIV Prevention Work in the U.S.? Experts Answer Your Questions

Timing of PrEP Before and After Sex Participants in a pre-exposure prophylaxis (PrEP) trial comparing TDF/FTC (Truvada) with a look-alike dummy pill aimed to take two pills 2 to 24 hours before sex, one pill 24 hours after the first two pills, and one pill 24 hours after the third pill.
The Center for AIDS Information & Advocacy

The evidence is already three years old: As posted on TheBodyPRO in February 2016, researchers reported the results of a study among 400 gay men in France and Canada showing efficacy of an "on-demand" approach for short-term pre-exposure prophylaxis (PrEP). In that placebo-controlled study, men taking two pills of emtricitabine/tenofovir disoproxil fumarate (TDF/FTC, branded as Truvada in the U.S.) two to 24 hours before sex, followed by a third pill 24 hours later and a fourth pill 24 hours after that, were completely protected against HIV infection, as compared to their peers not taking PrEP.

The efficacy of on-demand PrEP is also uncontroversial, compelling enough that clinical guidance in Australia, Canada, and Europe now include the option of the three-day 2-1-1 "on-demand" PrEP sequence alongside the option of a daily PrEP regimen for men who have sex with men (MSM). For clinicians in the U.S., the International Antiviral Society-USA (IAS-USA) has also endorsed the option of the 2-1-1 PrEP regimen.

But work is still needed to inform clinicians, PrEP programs, and other HIV programs serving communities of color in the U.S. This was the central theme of a panel discussion about on-demand PrEP at the recent December 3-4 Biomedical HIV Prevention Summit, held December 3 and 4 in Los Angeles.

Following a presentation at the summit by Bob Grant, M.D., M.P.H., with University of California at San Francisco (UCSF) about the proven efficacy of the 2-1-1 PrEP approach, presenters Shannon Weber, M.S.W., with PleasePrEPMe.org, and Joshua O'Neal, M.A., with Strut described the practical ways that those programs are supporting gay men and their providers to understand and consider intermittent PrEP as an option.

Dozens of hands were raised, and session participants asked a series of questions:

Q. The 2-1-1 on-demand PrEP regimen was found effective for gay men in high-income countries. Can it be used to protect other populations, such as women, trans people, people who inject drugs, or people in low-income settings?

A. Panelists agreed that more research is needed and is underway to define and confirm the effectiveness of on-demand PrEP as an option for multiple populations and settings. On-demand PrEP was not evaluated for women and is not currently being studied as an option for women, in part because the dynamics of protection in vaginal tissues are different from those in anal and rectal tissues. Among people at risk through anal sex or unsafe injection practices, not everyone can predict the times when they might need protection against HIV, and not everyone is able or ready to hold pills and use them in a timed sequence related to potential exposure. However, taking a long-term daily pill may also be challenging, and a 2-1-1 PrEP regimen could be an important option for individuals whose potential HIV exposure and PrEP needs fluctuate over time.

Q. Can clinicians advise and prescribe PrEP for on-demand use? Can PrEP educators and PrEP navigators recommend 2-1-1 dosing?

A. Grant acknowledged that the U.S. Food and Drug Administration (FDA)'s approval and Centers for Disease Control and Prevention guidelines for PrEP are for daily use but stated that it is entirely legal and very common for clinicians to recommend and prescribe medicines for "off-label" uses beyond what is described in the FDA approval, based on a broad knowledge of published literature and recommendations of leading medical associations Panelist Shannon Weber encouraged participants to visit PleasePrEPMe.org to ask questions through an online chat function and to find protocols for providers to counsel people about on-demand PrEP. HIV advocates and people needing PrEP should actively help providers to understand the evidence, not only about efficacy and safety of PrEP but also about the benefit of HIV testing and other sexually transmitted infection (STI) screening that accompanies PrEP.

Q. Why hasn't Gilead, the company selling TDF/FTC under the brand name Truvada, applied to the FDA for approval of Truvada for on-demand use?

A. James Rooney, M.D., vice president of Medical Affairs with Gilead Sciences, was in the audience and, prompted to respond, stated that while Gilead believes the evidence about the efficacy of on-demand PrEP is robust and convincing, Gilead has other priorities related to the licensing and sale of its newer tenofovir-containing drug TAF (brand name Descovy).

Ultimately, participants agreed that on-demand PrEP should be widely discussed as an option for gay men and other men who have sex with men. The U.S. Preventive Services Task Force (USPSTF) has given an "A" rating to PrEP as a primary HIV prevention intervention, supporting PrEP's integration into routine clinical practice and standard insurance coverage. Community HIV advocates have called for a rapid scaling up of PrEP access and usage as a crucial part of ending the HIV epidemic in the U.S.

Scale-up of PrEP access and use requires many things: a national commitment for federally-funded PrEP services, improved access to health insurance coverage, affordable PrEP pricing, PrEP access through Title X programs, substance use treatment and harm reduction programs, family and youth services, school health programs, and other programs currently offering HIV testing and follow-up care.

As a part of that, a simple three-day four-pill regimen, the 2-1-1, is an important option.