Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

Abstract

Background: Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis.

Methods: Phase 2 48-week safety/tolerability study was conducted, comparing 4 regimens: MVC alone, MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. Eligible participants were HIV-uninfected men and transgender women reporting condomless anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days. At each visit, assessments, laboratory testing, and counseling were done. Analyses were intention to treat.

Results: Among 406 participants, 84% completed follow-up, 7% stopped early, and 9% were lost to follow-up; 9% discontinued their regimen early. The number discontinuing and the time to discontinuation did not differ among study regimens (P = .60). Rates of grade 3-4 adverse events did not differ among regimens (P = .37). In a randomly selected subset, 77% demonstrated detectable drug concentrations at week 48. Five participants acquired HIV infection (4 MVC alone, 1 MVC + TDF; overall annualized incidence, 1.4% [95% confidence interval, .5%-3.3%], without differences by regimen; P = .32); 2 had undetectable drug concentrations at every visit, 2 had low concentrations at the seroconversion visit, and 1 had variable concentrations.

Conclusions: MVC-containing regimens were safe and well tolerated compared with TDF + FTC; this study was not powered for efficacy. Among those acquiring HIV infection, drug concentrations were absent, low, or variable. MVC-containing regimens may warrant further study for pre-exposure prophylaxis.

Clinical trials registration: NCT01505114.

Keywords: HIV; PrEP; maraviroc; men who have sex with men (MSM); phase 2 clinical trial.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Figures

Figure 1.

Trial profile. Abbreviations: FTC, emtricitabine; MVC, maraviroc; TDF, tenofovir disoproxil fumarate.

Figure 2.

Time to permanent study discontinuation and shown by Kaplan–Meier plot. Abbreviations: FTC, emtricitabine; MVC, maraviroc; TDF, tenofovir disoproxil fumarate.

Figure 3.

Estimated incidence of human immunodeficiency virus (HIV) infection by study arm, calculated using the exact method for Poisson counts. The overall HIV incidence was 1.4% (95% confidence interval [CI], .5%–3.3%), without differences among the study arms (P = .32). Abbreviations: FTC, emtricitabine; MVC, maraviroc; TDF, tenofovir disoproxil fumarate.

Figure 4.

Study drug plasma concentrations over time in participants experiencing human immunodeficiency virus (HIV) seroconversion. Each line presents data from a unique participant who acquired HIV infection and had detectable study drug plasma concentrations; all 3 were randomized to the maraviroc (MVC)–alone arm. Note: 2 other participants who acquired HIV infection, 1 randomized to MVC and 1 to MVC plus tenofovir disoproxil fumarate, had undetectable study drug concentrations at every study visit and are not shown. Diamond points represent study visits at which HIV seroconversion was documented. Boxed points represent visits at which HIV RNA was detected retrospectively; HIV antibody test results at that visit were negative or nonreactive. The expected predose, steady-state geometric mean concentration with MVC dosed at 300 mg/d is 32 ng/mL [31].