No woman taking daily maraviroc pre-exposure prophylaxis (PrEP) with or without tenofovir (TDF, Viread) or emtricitabine (FTC, Emtriva) became infected with HIV through 48 weeks in a randomized, double-blind, 188-woman U.S. study. Daily TDF/FTC (Truvada), the only regimen approved to date for PrEP in the United States, also protected all women assigned to that combination. The study results were presented at AIDS 2016.
In a parallel study reported at CROI 2016 in U.S. men who have sex with men, five of 406 men using maraviroc-based daily PrEP regimens acquired HIV infection. All five men who became infected had low or no detectable PrEP drug levels.
The phase-2 HPTN 069/ACTG A5305 trial was the first randomized interventional study of HIV PrEP in U.S. women. At 12 HPTN and ACTG sites, researchers recruited HIV-negative women with a history of condomless vaginal or anal sex in the past 90 days with an HIV-positive or HIV status-unknown man. The study excluded women who injected drugs and required all participants to have a creatinine clearance ≥70 mL/minute.
The HPTN/ACTG team randomized enrollees to one of four oral, once-daily regimens: (1) 300 mg of maraviroc alone, (2) maraviroc plus 200 mg of FTC, (3) maraviroc plus 300 mg of TDF, or TDF/FTC. With a matching placebo for each agent, all regimens consisted of three pills. All analyses were intention-to-treat.
The trial involved 188 women with a median age of 35 years (range 18 to 61). Most participants, 65%, were black, while 27% were white and 17% Latina. More than half of these women, 54%, had some college or more education. Seven women (4%) had a sexually transmitted infection (STI) at screening. Of the 188 women randomized, 186 began study drugs and 160 completed the trial.
Trial arms did not differ in the proportion of women who discontinued study drugs or time to permanent drug discontinuation. Nor did the arms differ in proportions of women with grade 3 or 4 adverse events, 48 of which affected 35 women (19%). Researchers regarded 11 of the 48 events related to study drugs. During follow-up, four women (2%) had a new STI diagnosed.
Adherence to PrEP pills was moderately high throughout the study. Ninety-one of 141 samples (65%) had all study drugs in the regimen detectable at week 24, as did 75 of 126 (60%) at week 48. Adherence monitored by drug level did not differ significantly between study arms. No woman on any PrEP regimen became infected through 48 weeks to yield an annual incidence of 0% (95% confidence interval 0% to 2.5%).
The HPTN/ACTG investigators proposed that "maraviroc-containing regimens could be considered for testing in HIV PrEP clinical efficacy trials."