On-Demand Prevention in France: A Top HIV Clinical Development of 2018
We know HIV pre-exposure prophylaxis (PrEP) works, but is daily dosing really necessary? For many, the dictum of a "pill a day keeps the HIV away" is just fine. Yet, some have a harder time taking medications daily.
A few years ago, the IPERGAY study planted the idea of an alternative PrEP strategy, demonstrating high-level protection from HIV transmission with "on-demand" PrEP -- dosing of emtricitabine/tenofovir disoproxil fumarate (Truvada, TDF/FTC) before sex (two tablets taken 2 to 24 hours prior) and then after (one tablet 24 hours, and another 48 hours, after first dose). That trial was relatively small at 361 participants enrolled.
At the 2018 International AIDS Conference this summer, the same investigators presented interim findings from Prévenir, an on-going study that will enroll 3,000 HIV-negative people with an indication for PrEP in the Paris region. In a creatively twist, participants are given the choice of which approach they want, daily dosing or the IPERGAY dosing, rather than be randomized; in addition, switching between strategies is allowed. The study primarily aims to show, with either strategy being available, a 15% or more dent in new diagnoses of HIV in the greater Paris region.
Preliminary data including the first 1,628 participants enrolled (99% of whom are men who have sex with men) were presented. On-demand PrEP was selected by 54%; interestingly, at baseline these participants reported less risky behaviors relative to those who opted for daily PrEP. During a mean seven months of follow-up, people generally stuck with their selected option and were pretty good at using it as directed. There was plenty of sex, including condomless sex, although more so in the daily PrEP group.
So far, no cases of HIV seroconversion have occurred with either daily or on-demand PrEP, and no participant has stopped PrEP due to an adverse event. Extrapolating from the seroconversion rate of the IPERGAY trial, the investigators calculate that 85 cases of HIV transmission have been averted in Prévenir to date.
The Bottom Line
On-demand PrEP, like Jerry Lewis and Mickey Rourke, may be big in France, but in the U.S., not so much. Heck, we have our hands full just getting many primary care providers to know what PrEP is, and the data supporting on-demand PrEP, thus far, have been limited. But with the interim findings from Prévenir, we need to look at how to use this strategy to help get PrEP to more who can benefit from it.
This means departing from our tendency to protocol-ize PrEP. Fear-based dogma that necessitate strict adherence to clinic visits every three months and over-aggressive lab testing are creating barriers to PrEP. Prévenir importantly allows individuals to customize their PrEP, and we can learn a lesson from this thinking.
Clinics that provide PrEP can also develop ways to de-medicalize and streamline the process. For example, for the busy university student who has demonstrated reasonable adherence to PrEP and evaluations, it is not sacrilegious to consider providing them four, or even six, PrEP refills along with instructions to get tested for HIV and sexually transmitted infections at their local health department in between clinic visits. Results can be sent through an electronic medical record portal or other secure method. The kind of reason and creativity that has been demonstrated by the Prévenir team can help us get PrEP to the next level in the U.S.
David Alain Wohl, M.D., is a professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC). He is site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, director of the North Carolina AIDS Education and Training Center (AETC), and co-director of HIV services for the North Carolina state prison system. In 2014, he became co-director of the UNC-Duke Clinical RM Ebola Response Consortium.