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).
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.


BACKGROUND
NCT01505114.
Department of Medicine, Weill Cornell Medicine, New York.
Roy M
RM
Gulick
Department of Medicine, Weill Cornell Medicine, New York.
Timothy J
TJ
Wilkin
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center.
Ying Q
YQ
Chen
Department of Medicine, University of California, Los Angeles.
Raphael J
RJ
Landovitz
Department of Health Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor.
K Rivet
KR
Amico
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center.
Alicia M
AM
Young
Department of Pathology.
Paul
P
Richardson
Department of Medicine, Johns Hopkins University School of Medicine.
Mark A
MA
Marzinke
Department of Medicine, Johns Hopkins University School of Medicine.
Craig W
CW
Hendrix
Department of Pathology.
Susan H
SH
Eshleman
Department of Medicine, University of Pittsburgh School of Medicine.
Ian
I
McGowan
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center.
Leslie M
LM
Cottle
Department of Medicine, Johns Hopkins University School of Medicine.
Adriana
A
Andrade
Department of Medicine, University of North Carolina, Chapel Hill.
Cheryl
C
Marcus
HIV Research Branch.
Karin L
KL
Klingman
Clinical Prevention Research Branch, Prevention Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Wairimu
W
Chege
ViiV Healthcare.
Alex R
AR
Rinehart
Gilead Sciences, Foster City.
James F
JF
Rooney
FHI 360, Durham, North Carolina.
Philip
P
Andrew
Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
Robert A
RA
Salata
Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University.
Manya
M
Magnus
Johns Hopkins University School of Nursing, Baltimore.
Jason E
JE
Farley
Bridge HIV, San Francisco Department of Public Health, California.
Albert
A
Liu
Department of Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia.
Ian
I
Frank
Department of Medicine, University of Pittsburgh School of Medicine.
Ken
K
Ho
Department of Medicine, University of Puerto Rico School of Medicine, San Juan.
Jorge
J
Santana
Department of Medicine, University of Washington, Seattle.
Joanne D
JD
Stekler
FHI 360, Washington, DC.
Marybeth
M
McCauley
Fenway Health, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts.
Kenneth H
KH
Mayer
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects; D065100:CCR5 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects*; D003510:Cyclohexanes / Q000008:administration & dosage* / Q000009:adverse effects*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004311:Double-Blind Method; D015658:HIV Infections / Q000517:prevention & control*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D011446:Prospective Studies; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D055815:Young Adult
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc
HIV; PrEP; maraviroc; men who have sex with men (MSM); phase 2 clinical trial