Maraviroc (MVC) is an HIV entry inhibitor that concentrates in the genital tract/rectum and can be given orally once-daily, making it a possible alternative PrEP agent.
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 (pts) were adult HIV-uninfected men who reported a history of condomless anal intercourse with >1 HIV-infected or unknown-status man within 90 days, and had adequate safety laboratory parameters including calculated creatinine clearance >70 ml/min. Pts received randomized study regimens for 48 weeks with follow-up visits at weeks 2, 4, 8, and then every 8 weeks. At each study visit, interval history, physical exam, safety laboratories, blood plasma for drug levels, and HIV and adherence counseling and testing were conducted. All analyses were intent-to-treat; primary analyses used Kaplan-Meyer survival analysis and comparisons between study arms used chi-square, t-test, or log-rank testing.
12 HPTN and ACTG sites enrolled 406 men with a median age of 30 (range 18-70; 30% <26), including 28% black, 62% white, and 10% other races; with 22% Latino. 340 (84%) completed study follow-up; 38 (9%) were lost to follow-up. 37 (9%) permanently discontinued the study regimen prior to 48 weeks; time to discontinuation did not differ among the study arms (p=0.6). The rates of grade 2-4 adverse events did not differ in pairwise comparisons between the study arms (p>0.5). Calculated creatinine clearance decreased 3-8 ml/min from baseline to week 48, without differences among the study arms (p=0.6). In a random subset of participants (n=122) at random study time points, 93% had detectable study drug plasma levels. 5 HIV seroconversions occurred: 2 had no detectable study drug levels at any study visit (1 on MVC alone, 1 on MVC+TDF), 3 others (all on MVC alone) had MVC levels of 0.7, 6.7, and 145 ng/ml (limit of quantification 0.5) at the documented seroconversion study visit; all had R5 virus and none had genotypic resistance.
Given as HIV PrEP in MSM, MVC-based regimens were comparably safe and well-tolerated versus the control regimen of TDF+FTC. Of 5 seroconversions, 4 were associated with low or undetectable drug levels. MVC regimens may be alternatives for oral PrEP.