article260

ANRS IPERGAY

"Antiretroviral Preexposure Prophylaxis for HIV Prevention in Men Who Have Sex with Men". The New England Journal of Medicine. 2015. ClinicalTrials.gov number, NCT01473472.

Clinical Question

Does the use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) before and after sexual activity provide protection against HIV-1 infection in men who have unprotected anal sex with men?

Bottom Line

In men who have sex with men and engage in unprotected anal sex, the use of TDF-FTC before and after sexual activity reduced the incidence of HIV-1 infection with a relative reduction of 86% in the risk of HIV-1 infection.

Major Points

Several previous trials have yielded inconsistent results on the efficacy of daily antiretroviral preexposure prophylaxis (preP) for HIV prevention, potentially due to low adherence to the regimen. The IPERGAY trial investigated the use of a sexual activity-dependent regimen of TDF-FTC as preP among high-risk men who have sex with men. This study found an 86% relative reduction in the risk of HIV-1 infection in individuals taking TDF-FTC around the time of sexual activity compared to placebo.

Guidelines

The use of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have sex with men is recommended as a prevention strategy, alongside consistent condom use and other behavioral interventions.

Design

Multicenter, double-blind, parallel group, randomized, placebo-controlled trial. Participants were randomly assigned to take TDF-FTC or placebo before and after sexual activity. Follow-up was a median of 9.3 months, with all participants receiving risk-reduction counseling and condoms, and they were regularly tested for HIV-1, HIV-2, and other sexually transmitted infections.

Population

414 participants underwent randomization, and 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group).

Inclusion Criteria
Male sex with an age of at least 18 years, history of unprotected anal sex with at least two partners in the past 6 months, HIV-negative status.

Exclusion Criteria
Positive for hepatitis B surface antigen, chronic hepatitis C virus infection, creatinine clearance <60 ml per minute, alanine aminotransferase level >2.5 times the upper limit of normal range, glycosuria or proteinuria >1+ on urine dipstick testing.

Interventions

Participants took a combination of 300 mg TDF and 200 mg FTC or placebo based on sexual activity, with a loading dose taken 2 to 24 hours before sex followed by doses 24 and 48 hours after the first intake.

Outcomes

Primary Outcome
HIV-1 infection diagnosed with a fourth-generation enzyme-linked immunosorbent assay (ELISA) or HIV-1 RNA polymerase-chain-reaction (PCR) assay. 16 HIV-1 infections occurred in the follow-up period: 2 in the TDF-FTC group (incidence of 0.91 per 100 person-years) and 14 in the placebo group (incidence of 6.60 per 100 person-years), illustrating a relative reduction in the TDF-FTC group of 86%.

Secondary Outcomes
The number of sexual partners and incidence of sexually transmitted infections during the follow-up were similar in both groups. Reported adverse events included gastrointestinal and renal events which were higher in the TDF-FTC group.

Criticisms

Assessing adherence to on-demand preP is challenging. The efficacy result may be exaggerated due to high initial adherence, and long-term toxicity effects of TDF-FTC could not be assessed. Additionally, the efficacy in men who have sex with men with less frequent sexual activity is unclear.

Funding

The National Agency of Research on AIDS and Viral Hepatitis (ANRS), the Canadian HIV Trials Network, the Fonds de Dotation Pierre Bergé pour la Prévention, and the Bill and Melinda Gates Foundation. Gilead Sciences donated the study medications and provided funding for the pharmacokinetics analysis.