A pill for HIV prevention: to take when you need it

On-demand preexposure prophylaxis in men at high risk for HIV-1 infection.

Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Preau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Dore V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF, Group AIS. N Engl J Med. 2015 Dec 3;373(23):2237-46. doi: 10.1056/NEJMoa1506273. Epub 2015 Dec 1.

Background: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen.

Methods: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections.

Results: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03).

Conclusions: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events.

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Editor’s notes: The IPERGAY trial is the first trial to assess ‘on demand’ HIV pre-exposure prophylaxis (PrEP). It had a ‘take it when you need it’ approach, rather than a daily dosing approach where a pill is taken every day, regardless of sexual activity. In 2010, the iPrEx Trial of daily pills among gay men and other men who have sex with men reported a 42% relative reduction in HIV incidence. In participants with detectable drug in their blood (meaning that they had been taking the pills), the reduction was 92%. The IPERGAY researchers set out to prove or disprove the hypothesis that men would be more likely to take pills if pill-taking was associated with having sex. The hypothesis was that this might improve adherence and hence reduce the risk of HIV acquisition compared with daily dosing. Participants were randomly assigned to take a dose of two pills of TDF/FTC (tenofovir disoproxil fumarate/emtricitabine) or placebo with food between two and 24 hours before sex. A third pill was taken 24 hours after sex and a fourth pill 24 hours after that. If they continued to be sexually active, they were told to take one pill a day while sexually active and then the two post-exposure doses 24 hours apart. When the striking results of the PROUD trial in the United Kingdom, among gay men and other men who have sex with men, were made public [see HIV This Month February 2015], IPERGAY’s Data Safety and Monitoring Board (DSMB) asked for an unblinded interim analysis of the IPERGAY data. The results were so convincing (an 86% relative risk reduction) that the DSMB recommended that the trial be unblinded so that men in the placebo arm could be offered active drug. The next question was whether this highly effective preventive measure could be made available outside the trial setting. The Food and Drug Administration of the United States of America had approved TDF/FTC for HIV PrEP in 2012 but no country had followed suit. On November 23, 2015, France’s Minister for Social Affairs, Health, and Women’s Rights announced a temporary recommendation for the use of TDF/FTC HIV prophylaxis, opening the way to the authorisation of PrEP in other European countries. Before any other European country responded, South Africa’s Medicines Control Council announced on December 3, 2015 its approval of the fixed-dose combination of TDF/FTC for pre-exposure prophylaxis of HIV. Kenya’s Pharmacy & Poisons Board also approved once-daily use of TDF/FTC for HIV prevention on December 23, 2015. The scientific evidence has been building for years. Clearly it is time to act now to make this highly effective HIV prevention choice available to people at highest risk of HIV exposure.

Europe, Northern America
Canada, France
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