Does On-Demand PrEP Prevent HIV?


On-demand PrEP before and after sexual activity could reduce the incidence of HIV-1 in men who have sex with men.

Although 100% daily adherence is advised for pre-exposure prophylaxis (PrEP) to prevent HIV transmission, a recent study discovered that on-demand PrEP before and after sexual activity could reduce the incidence of HIV-1 in men who have sex with men.1

This double-blind, randomized trial compared the efficacy of tenofovir/emtricitabine (Truvada) with placebo before and after sexual activity in men engaging in unprotected anal intercourse with at least 2 male partners in the preceding 6 months. PrEP was administered as a fixed-dose combination of tenofovir 300 mg/emtricitabine 200 mg.

Each participant took a loading dose of 2 tablets of tenofovir/emtricitabine or placebo with food at least 2 to 24 hours prior to sexual activity. A third tablet was administered 24 hours after the loading dose and a fourth tablet 24 hours later. All participants also received education on HIV risk reduction and condom use, as well as testing for HIV infection and sexually transmitted infections (STIs).

Four hundred patients without HIV infection were followed for a median of 9.3 months. Participants took a median of 15 pills of the study agent per month.

Just 2 participants in the 199-patient PrEP group developed HIV-1 infection (incidence=0.91 per 100 person-years) compared with 14 participants in the 201-patient placebo group (incidence=6.60 per 100 person-years), yet none developed resistance to the study medication. There was no change in sexual practices where 41% of the tenofovir/emtricitabine group and 33% of the placebo group acquired new STIs (p=0.10).

In the PrEP group, the relative risk reduction was 86% (p=0.002). This group experienced higher rates of gastrointestinal (GI) (14% vs. 5%, p=0.002) and renal adverse events (18% vs. 10%, p=0.03).

The authors concluded that on-demand PrEP before and after sexual activity reduced the incidence of HIV-1 in men who have sex with men, but it was associated with more GI and renal adverse events. Although the study duration was relatively short, it provides promising evidence that daily adherence to PrEP may not be necessary.

Post-hoc analyses of a previous study suggested that taking at least 4 continuous doses of PrEP weekly demonstrated no development of HIV-1 infections in men who have sex with men.

One major limitation of PrEP use is the potential to still transmit or receive an STI. Although the reduction of HIV may occur, unprotected sexual encounters leave participants at risk for syphilis, gonorrhea, and chlamydia.

The US Centers for Disease Control and Prevention recently reported that STIs are on the rise for the first time since 2006. The rates of syphilis, gonorrhea, and chlamydia rose by 15.1%, 5.1%, and 2.8%, respectively.

Although STI risk reduction and condom use is stressed upon receipt of PrEP, it still remains a great concern in this population because STIs may cause inflammation or lesions that may increase the risk of acquiring HIV.2

Even though this study demonstrates promising data for on-demand PrEP, patients at risk for HIV should still be educated on risk reduction techniques, the importance of condom use, and the need to stay adherent to current PrEP prescribing habits.


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;373:2237-46.

2. Ward H, Rönn M. Contribution of sexually transmitted infections to the sexual transmission of HIV. Curr Opin HIV AIDS. 2010 Jul;5:305-10. doi: 10.1097/COH.0b013e32833a8844.

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