Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women: A phase 2 randomized trial
Citation: Gulick RM, Wilkin TJ, Chen YQ, Landovitz RJ, Amico KR, 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, Siegel M, Manabe YC, Frank I, Ho K, Santana J, Stekler JD, Swaminathan S, McCauley M, Hodder S, Mayer KH. Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women: A phase 2 randomized trial. Ann Intern Med 2017 Sep 19;167(6):384-393. PMC5667908
Access full article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667908/
BACKGROUND
Maraviroc (MVC) is a candidate drug for HIV PrEP.
OBJECTIVE
To assess the safety/tolerability of MVC-containing PrEP in U.S. women at-risk for HIV over 48 weeks.
DESIGN
Phase 2 randomized, controlled, double-blinded study of four PrEP regimens (#NCT01505114).
SETTING
Twelve clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group.
PARTICIPANTS
HIV-uninfected women reporting condomless vaginal or anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days.
INTERVENTIONS
MVC alone, MVC+emtricitabine (FTC), MVC+tenofovir disoproxil fumarate (TDF), and TDF+FTC (control).
MEASUREMENTS
At each visit, clinical and laboratory (including HIV) assessments were conducted. Primary outcomes were grade 3–4 adverse events and time to permanent regimen discontinuation. Analyses were conducted on all randomized participants, according to original regimen assignment.
RESULTS
Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost-to-follow-up; 19% discontinued their regimen prematurely. Number discontinuing and time-to-discontinuation did not differ among regimens. Grade 3/4 adverse events occurred in 5 (MVC), 13 (MVC+FTC), 9 (MVC+TDF) and 8 (TDF+FTC) participants; rates did not differ among regimens. One death occurred (suicide; MVC+FTC), judged not regimen-related. Of available samples at week 48 (n=126), 60% demonstrated detectable drug concentrations. No new HIV infections occurred.
LIMITATIONS
Participants were not necessarily high-risk for HIV. Regimen was 3 pills daily. Study was not powered for efficacy.
CONCLUSIONS
MVC-containing PrEP regimens were safe and well-tolerated compared to the control regimen of TDF+FTC in U.S. women. No new HIV infections occurred, although whether this was due to low risk of the population or to protection from the study regimens is not certain. MVC-containing PrEP for women may warrant further study.