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.

• Authors: Roy M Gulick, Timothy J Wilkin, Ying Q Chen, Raphael J Landovitz, K Rivet Amico, Alicia M Young, Paul Richardson, Mark A Marzinke, Craig W Hendrix, Susan H Eshleman, Ian McGowan, Leslie M Cottle, Adriana Andrade, Cheryl Marcus, Karin L Klingman, Wairimu Chege, Alex R Rinehart, James F Rooney, Philip Andrew, Robert A Salata, Manya Magnus, Jason E Farley, Albert Liu, Ian Frank, Ken Ho, Jorge Santana, Joanne D Stekler, Marybeth McCauley, Kenneth H Mayer
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 215 Issue 2 Pg. 238-246 (Jan 15 2017) ISSN: 1537-6613 [Electronic] United States
• PMID: 27811319 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Anti-HIV Agents
• CCR5 Receptor Antagonists
• Cyclohexanes
• Triazoles
• Maraviroc

Topics

• Adolescent
• Adult
• Aged
• Anti-HIV Agents (administration & dosage, adverse effects)
• CCR5 Receptor Antagonists (administration & dosage, adverse effects)
• Cyclohexanes (administration & dosage, adverse effects)
• Disease Transmission, Infectious (prevention & control)
• Double-Blind Method
• HIV Infections (prevention & control)
• Homosexuality, Male
• Humans
• Male
• Maraviroc
• Middle Aged
• Pre-Exposure Prophylaxis (methods)
• Prospective Studies
• Triazoles (administration & dosage, adverse effects)
• Young Adult