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As-Needed PrEP Cuts HIV Rate 86% in French-Canadian Ipergay Trial
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CROI 2015, February 23-26, 2015, Seattle, Washington
Mark Mascolini
http://www.croiwebcasts.org/console/player/25539?mediaType=slideVideo&
Taking tenofovir/emtricitabine (TDF/FTC) PrEP twice before and twice after sex slashed HIV incidence 86% in the 400-person double-blind placebo-controlled Ipergay trial, which enrolled gay and bisexual men [1]. The only 2 men in the TDF/FTC arm who became infected with HIV reported not taking their PrEP pills for months while continuing regular sex.
Preexposure prophylaxis (PrEP) trials reported so far yield varying results reflecting adherence to the daily TDF/FTC regimens used. Good adherence has invariably yielded high protection from HIV. French ANRS investigators reasoned that taking TDF/FTC only before planning sex and immediately afterwards would be easier for PrEP candidates than taking a pill every day. On the basis of macaque studies, they devised a regimen calling for 2 TDF/FTC pills 2 to 24 hours before sex, 1 pill 24 hours later and another pill 48 hours after the first dose. The investigators call this "on-demand" dosing, though "as-needed" dosing may be a more precise term.
Jean-Michel Molina and colleagues recruited more than 400 HIV-negative men who reported condomless anal sex with at least 2 partners in the past 6 months. They randomized men to as-needed TDF/FTC or to placebo and included 199 men taking TDF/FTC and 201 taking placebo in a modified intention-to-treat analysis. Nearly 90% of men in each arm remained in follow-up.
Median age stood at 35 in the TDF/FTC arm and 34 in the placebo arm, 95% and 92% were white, 91% and 89% completed secondary education, and 85% and 84% had a job. About one quarter of enrollees had a recent sexually transmitted infection (STI), median number of sex acts in the past 4 weeks stood at 10, and median number of partners in the past 2 months totaled 8.
In October 2014 Ipergay's Data and Safety Monitoring Board recommended halting the placebo arm and offering all men as-needed PrEP. When Molina and colleagues analyzed the data at an average follow-up of 13 months, they counted 2 HIV infections in the TDF/FTC group and 14 in the placebo group for an incidence of 0.94 per 100 person-years with TDF/FTC and 6.6 per 100 person-years with placebo. Statistical analysis determined an 86% relative reduction in HIV incidence with TDF/FTC (95% confidence interval 40% to 99%, P = 0.002). Number needed to treat for 1 year to prevent 1 infection was 18.
Adherence measured by pill count was the same in the two study arms, a median of 16 pills per month. Forty-eight men (12%) took postexposure prophylaxis during the trial, 13% in the TDF/FTC arm and 11% in the placebo arm.
Adverse event rates were generally similar with TDF/FTC and placebo, with 92% and 89% reporting any adverse event, 9% and 8% having a serious adverse event, and 9% and 7% having any grade 3 or 4 adverse event. Drug-related gastrointestinal problems proved more frequent with TDF/FTC than with placebo (13% versus 6%, P = 0.013).
The high HIV incidence in the placebo arm--more than 6 of every 100 men infected every year--surprised the Ipergay team. Molina noted, though, that this incidence reflects the high-risk population recruited and high STI rates in these men: one third had one or more STIs during the study.
Ipergay investigators concluded that good adherence in the trial indicates support for an as-needed PrEP regimen, at least in a gay group like this. Although the researchers based the 4-dose regimen on reasonable data, Molina conceded he didn't know if they picked the best way to take TDF/FTC PrEP. Nevertheless, he stressed, it worked.
Reference
1. Molina JM, Capitant C, Spire B, et al. On demand PrEP with oral TDF-FTC in MSM: results of the ANRS Ipergay trial. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 23.
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