Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2017 Jan 15;215(2):238-246.
doi: 10.1093/infdis/jiw525.

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)

Roy M Gulick  1 , Timothy J Wilkin  1 , Ying Q Chen  2 , Raphael J Landovitz  3 , K Rivet Amico  4 , Alicia M Young  2 , Paul Richardson  5 , Mark A Marzinke  6 , Craig W Hendrix  6 , Susan H Eshleman  5 , Ian McGowan  7 , Leslie M Cottle  2 , Adriana Andrade  6 , Cheryl Marcus  8 , Karin L Klingman  9 , Wairimu Chege  10 , Alex R Rinehart  11 , James F Rooney  12 , Philip Andrew  13 , Robert A Salata  14 , Manya Magnus  15 , Jason E Farley  16 , Albert Liu  17 , Ian Frank  18 , Ken Ho  7 , Jorge Santana  19 , Joanne D Stekler  20 , Marybeth McCauley  21 , Kenneth H Mayer  22
Affiliations
Clinical Trial

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)

Roy M Gulick et al. J Infect Dis. .

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Trial profile. Abbreviations: FTC, emtricitabine; MVC, maraviroc; TDF, tenofovir disoproxil fumarate.
Figure 2.
Figure 2.
Time to permanent study discontinuation and shown by Kaplan–Meier plot. Abbreviations: FTC, emtricitabine; MVC, maraviroc; TDF, tenofovir disoproxil fumarate.
Figure 3.
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.
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].
See this image and copyright information in PMC

References

    1. Beyrer C, Baral SD, Collins C et al. . The global response to HIV in men who have sex with men. Lancet 2016; 388:198–206. - PubMed
    1. Grant RM, Lama JR, Anderson PL et al. . Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 363:2587–99. - PMC - PubMed
    1. McCormack S, Dunn DT, Desai M et al. . Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2016; 387:53–60. - PMC - PubMed
    1. Molina JM, Capitant C, Spire B et al. . On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015; 373:2237–46. - PubMed
    1. US Centers for Disease Control and Prevention. Recommendations for HIV prevention for adults and adolescents with HIV in the United States, 2014. http://www.cdc.gov/hiv/guidelines/index.html Accessed 24 November 2015.

Publication types

MeSH terms

Associated data