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TDF/FTC PrEP Durable in MSM, But MSM and Transgender Responses Differ
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
An update of results from the iPrEx trial of tenofovir/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) and transgender women who have sex with men determined that people taking TDF/FTC had a 45% lower risk of acquiring HIV infection than people taking placebo [1]. But TDF/FTC was not protective in the small proportion of transgender women enrolled in the trial.
iPrEx investigators randomized 2499 HIV-negative MSM or transgender women who have sex with men to take TDF/FTC or placebo once daily [2]. Most study sites were in the United States and South America; there was one site in Cape Town, South Africa, and one in Chiang Mai, Thailand. All study participants were male at birth. Researchers tested participants regularly for HIV, and all enrollees received risk-reduction counseling, condoms, and care for sexually transmitted infections. Enrollees had a checkup every 4 weeks that included TDF/FTC pill counts and adherence counseling.
The updated analysis extended through August 2010, 4 months after the visit cutoff for the published analysis [2]. Besides updating efficacy results, the researchers also compared results in various subgroups because TDF/FTC efficacy may vary as a result of differences in adherence, drug interactions, drug penetration into tissues, or other reasons.
In an intention-to-treat analysis considering all HIV infections throughout follow-up, study participants taking TDF/FTC PrEP had a 45% lower risk of infection than those taking placebo (95% confidence interval [CI] 23% to 61%, P = 0.0005). In a modified intention-to-treat analysis that included available data for all participants except those with HIV RNA detected in their enrollment sample, participants taking TDF/FTC had a 42% lower risk of HIV infection (95% CI 18% to 60%, P = 0.002).
People who took TDF/FTC consistently enough to have measurable drug levels in blood had a 92% lower risk of HIV infection. The iPrEx investigators performed a case-control study comparing 48 participants who became infected with 144 controls who did not. Controls were matched to cases by study site and time in the study. Cases and controls had all been randomized to TDF/FTC. An analysis that factored in age, unprotected receptive anal intercourse at study entry and follow-up, schooling, and body mass index found consistently lower proportions of participants who became infected than controls who remained HIV-free had undetectable TDF in cells (9% versus 36%), TDF in plasma (8% versus 40%), FTC in cells (11% versus 41%), FTC in plasma (8% versus 40%), or any detectable drug (10% versus 44%).
The investigators found no evidence of resistance to TDF or FTC in virus from people who became infected during the trial. Viral load in participants who became infected did not differ between those taking TDF/FTC and those taking placebo. Lack of resistance and high viral loads in infected participants randomized to TDF/FTC indicated that these people had poor adherence to the daily regimen.
Rates of unprotected receptive anal intercourse did not differ between people randomized to TDF/FTC and those randomized to placebo over 156 weeks on study. PrEP protective efficacy was significantly higher in 1485 participants who reported receptive anal intercourse when the study began than in those who did not (59% versus 25%, P = 0.04). PrEP protective efficacy was higher in 332 participants circumcised when iPrEx began than in uncircumcised participants (83% versus 36%), though that difference fell short of statistical significance (P = 0.10). Protective efficacy of TDF/FTC did not differ by ethnicity, alcohol use, schooling, or age.
Among 366 participants (15%) who identified themselves as transgendered or who used female sex hormones, there were 11 HIV infections in the TDF/FTC group and 11 in the placebo group. Almost none the transgendered participants had had sex-change surgery. The iPrEx team speculated that differences in PrEP efficacy between transgendered and nontransgendered participants might be explained by chance or by differences in patterns of PrEP use, sexual practices, or hormonal effects on drug transport in the mucosa.
The investigators concluded that "oral FTC/TDF PrEP provides additional protection against the acquisition of HIV infection among MSM receiving a comprehensive package of prevention services." They stressed that protection from HIV acquisition was 92% in men taking TDF/FTC regularly, as indicated by detectable TDF and/or FTC levels in blood and cells. The iPrEx team noted that protection was "nearly 90% to 100%" at some sites.
An extension of the iPrEx trial in which all participants will take TDF/FTC aims to determine whether people will use PrEP more consistently now that three trials have demonstrated that it helps prevent HIV acquisition. This trial, iPrEx OLE (for open-label extension) is recruiting men who have sex with men and transgender women who have sex with men in the United States and South Africa, while sites in other countries seek regulatory approval. See http://www.iprexole.com/.
References
1. Grant R, McMahan V, Liu A, et al, for the iPrEx study team. Completed observation of the randomized placebo-controlled phase of iPrEx: daily oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who have sex with men. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract WELBC04.
2. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2011;363:2587-2599. http://www.nejm.org/doi/full/10.1056/NEJMoa1011205.
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