Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial.

TitleSafety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Women: A Phase 2 Randomized Trial.
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, Siegel M, Manabe YC, Frank I, Ho K, Santana J, Stekler JD, Swaminathan S, McCauley M, Hodder S, Mayer KH
JournalAnn Intern Med
Volume167
Issue6
Pagination384-393
Date Published2017 Sep 19
ISSN1539-3704
KeywordsAdolescent, Adult, Cyclohexanes, Double-Blind Method, Female, Follow-Up Studies, HIV Fusion Inhibitors, HIV Infections, Humans, Middle Aged, Patient Dropouts, Pre-Exposure Prophylaxis, Prospective Studies, Treatment Outcome, Triazoles, Young Adult
Abstract

Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP).

Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection.

Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114).

Setting: 12 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 at least 1 man with HIV infection or unknown serostatus within 90 days.

Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control).

Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment.

Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 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 (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred.

Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy.

Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroc-containing PrEP for women may warrant further study.

Primary Funding Source: National Institutes of Health.

DOI10.7326/M17-0520
Alternate JournalAnn. Intern. Med.
PubMed ID28828489
PubMed Central IDPMC5667908
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
U01 AI069423 / 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
UM1 AI069466 / AI / NIAID 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 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