HPTN 069/ACTG A5305: phase II study of maraviroc-containing regimens for HIV PrEP in United States (U.S.) women

Abstract

Background: Maraviroc (MVC) is an HIV entry inhibitor that concentrates in the genital tract/rectum, making it a potential PrEP agent. Methods: Prospective, randomized, double-blinded, multisite, safety/tolerability study of 4 regimens for HIV PrEP: (1) MVC alone; (2) MVC + emtricitabine (FTC); (3) MVC + tenofovir (TDF); (4) TDF + FTC. Study regimens consisted of 3 pills once-daily -- MVC 300 mg, FTC 200 mg, TDF 300 mg, with matching placebos. Eligible participants were adult HIV-uninfected women who reported a history of condomless vaginal or anal intercourse with >1 HIV-infected or unknown-serostatus man within 90 days of screening, and had adequate safety laboratory parameters including calculated creatinine clearance >70 ml/min. Participants were randomized to study regimens for 48 weeks with follow-up visits at weeks 2, 4, 8, and then every 8 weeks. At each visit, history, physical exam, safety laboratories, blood plasma for drug concentrations, adherence counseling, and HIV testing were conducted. All analyses were intent-to-treat. Results: 12 HPTN and ACTG sites enrolled 188 women with a median age of 35 (range 18-61), including 65% black, 27% white, and 17% Latina participants. 153 (81%) completed study follow-up; 15 (8%) were lost to follow-up. 37 (20%) permanently discontinued the study regimen early, including 16 (8%) for participant request and 10 (5%) for pregnancy; rates and times to study drug discontinuation did not differ among the study arms (both p>0.2). MVC-alone was associated with fewer grade 2-4 adverse events than either TDF-containing regimen (p< 0.01); MVC+FTC was associated with fewer events than MVC+TDF (p=0.02). In a random subset of participants (n=125) at random study time points, 66% had detectable study drug plasma concentrations. 4 women had sexually transmitted infections while on study (3 chlamydia, 1 gonorrhea.) No HIV infections were identified during the study; the annual HIV incidence in women on this study was 0% [95% CI: 0%, 2.5%]. Conclusions: In this study of HIV PrEP in women, MVC-containing regimens were safe and well-tolerated compared to the control regimen of TDF+FTC. Only 2/3 had detectable study drug concentrations, but no HIV infections were identified. MVC-containing regimens should be explored further as oral PrEP for women.