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).

TitlePhase 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).
Publication TypeJournal Article
Year of Publication2017
AuthorsGulick RM, Wilkin TJ, Chen YQ, Landovitz RJ, K Amico R, Young AM, Richardson P, Marzinke MA, Hendrix CW, Eshleman SH, McGowan I, Cottle LM, Andrade A, Marcus C, Klingman KL, Chege W, Rinehart AR, Rooney JF, Andrew P, Salata RA, Magnus M, Farley JE, Liu A, Frank I, Ho K, Santana J, Stekler JD, McCauley M, Mayer KH
JournalJ Infect Dis
Volume215
Issue2
Pagination238-246
Date Published2017 Jan 15
ISSN1537-6613
KeywordsAdolescent, Adult, Aged, Anti-HIV Agents, CCR5 Receptor Antagonists, Cyclohexanes, Disease Transmission, Infectious, Double-Blind Method, HIV Infections, Homosexuality, Male, Humans, Male, Middle Aged, Pre-Exposure Prophylaxis, Prospective Studies, Triazoles, Young Adult
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.

DOI10.1093/infdis/jiw525
Alternate JournalJ. Infect. Dis.
PubMed ID27811319
PubMed Central IDPMC5790146
Grant ListUM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069503 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UL1 TR001111 / TR / NCATS NIH HHS / United States
UL1 TR000005 / TR / NCATS NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UL1 RR024153 / RR / NCRR NIH HHS / United States
UL1 RR024996 / RR / NCRR NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI069415 / AI / NIAID NIH HHS / United States
P30 AI045008 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069481 / AI / NIAID NIH HHS / United States
P30 AI117970 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI068619 / AI / NIAID NIH HHS / United States
UM1 AI069465 / AI / NIAID NIH HHS / United States
UM1 AI068613 / AI / NIAID NIH HHS / United States
UM1 AI069419 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
UM1 AI068617 / AI / NIAID NIH HHS / United States