PRACTICE CHANGER
Offer patients at high risk for human immunodeficiency virus (HIV), particularly men who have sex with men, preexposure prophylaxis (PrEP) with a combination pill of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) on an on-demand basis to decrease HIV-1 infection rates.
Strength of recommendation
B: Based on one good quality randomized control trial.1
Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373:2237-2246.
ILLUSTRATIVE CASE
Your patient is a 31-year-old man who has sex with men. He is sexually active with several different partners. He asks you if there is anything he can do to decrease his risk of becoming infected with human immunodeficiency virus (HIV). Besides recommending condom use, what should you offer him?
In most high-income countries, including the United States, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).2 Without a vaccine, condom use has served as the primary method of preventing infection.
In 2014, the Centers for Disease Control and Prevention (CDC) began recommending daily use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in high-risk individuals, as a form of preexposure prophylaxis (PrEP).3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT]=46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.6 However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably because of the difficulty in getting patients to take the medication on a daily basis.7,8
While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.5 That is because, until now, there have been no studies demonstrating the effectiveness of PrEP used episodically and taken only around the time of potential exposure.
STUDY SUMMARY
Fewer pills improves adherence, reduces HIV infection rates
The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays (IPERGAY) study was a double-blind, multicenter study conducted in France and Canada that assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.1 The study hypothesis was that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk of HIV infection.
The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection. The investigators defined high risk as having a history of unprotected anal sex with at least 2 partners in the previous 6 months. Other inclusion criteria included age ≥18 years, and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance <60 mL/min, alanine aminotransferase level >2.5 times the upper limit of normal, and significant glycosuria or proteinuria.
The pill and visit schedule. After excluding those who withdrew consent, were lost to follow-up, or who acquired HIV-1 infection, the study participants (199 in the TDF-FTC group and 201 in the placebo group) were randomized to take TDF-FTC or placebo before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. The participants were instructed to take a loading dose of 2 pills of TDF-FTC or placebo with food 2 to 24 hours prior to intercourse, followed by a third pill 24 hours after taking the first 2 pills, and a fourth pill 24 hours after the third pill. If there were multiple consecutive days with episodes of sexual intercourse, participants were to take one pill on each of the days of intercourse, and then the 2 post-exposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the preexposure prophylaxis; otherwise, they were to begin again with 2 pills 2 to 24 hours prior to intercourse and repeat the protocol.
Study coordinators followed participants 4 and 8 weeks after enrollment, and then every 8 weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count and drug levels in plasma, as well as with an at-home, computer-assisted interview completed by each participant prior to each visit.
Participants received counseling from a peer community member and were offered preventative services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.
