@article{734e45f5cd534bdab1fcb51b3792f88a,
title = "Phase 2a Safety, Pharmacokinetics, and Acceptability of Dapivirine Vaginal Rings in US Postmenopausal Women",
abstract = "Background Postmenopausal women have unique sociobiological human immunodeficiency virus (HIV) risks. We evaluated the safety, pharmacokinetics, and acceptability of a microbicide dapivirine (DPV) vaginal ring (VR) versus placebo in postmenopausal women. Methods We enrolled 96 HIV-negative postmenopausal US women in a phase 2a double-blind, randomized (3:1) trial of monthly VRs containing 25 mg DPV or placebo used continuously for 12 weeks. We assessed safety by adverse events (AEs). DPV concentrations were quantified in plasma and vaginal fluid. Steady-state concentrations were analyzed at 4, 8, and 12 weeks using repeated measures ANOVA. We assessed acceptability by self-report. Results We found no differences in the proportion of women with related grade 2 or higher reproductive system AEs (DPV: 6/72 (8%), placebo: 3/24 (13%), P =.68) or grade 3 or higher AEs (DPV: 4/72 (6%), placebo: 0/24 (0%), P =.57). In the DPV arm, 2/72 (3%) declined to resume product use due to AEs. Median DPV concentrations in plasma (262.0 pg/mL at week 12) and vaginal fluid (40.6 ng/mg at week 12) were constant over 12 weeks and exceeded the in vitro 50% effective concentration by 5000-fold in vaginal fluid by week 4. VR acceptability was high; 84/93 (90%) {"}very much liked or liked{"} the VR. Conclusions DPV VRs were safe, well tolerated, and acceptable in postmenopausal women. Plasma concentrations were comparable to published data on DPV use in reproductive-age women (median plasma concentration: 264 pg/mL). Given the reassuring safety and pharmacokinetic data, the DPV VR is promising for preexposure prophylaxis in postmenopausal women. Clinical Trials Registration NCT02010593.",
keywords = "dapivirine, menopause, microbicide, pre-exposure prophylaxis, vaginal rings",
author = "Chen, {Beatrice A.} and Jingyang Zhang and Gundacker, {Holly M.} and Hendrix, {Craig W.} and Hoesley, {Craig J.} and Salata, {Robert A.} and Dezzutti, {Charlene S.} and {Van Der Straten}, Ariane and Hall, {Wayne B.} and Jacobson, {Cindy E.} and Sherri Johnson and Ian Mcgowan and Nel, {Annalene M.} and Lydia Soto-Torres and Marzinke, {Mark A.}",
note = "Funding Information: Potential conflicts of interest. A. N. is employed by International Partnership for Microbicides, the supplier of both the placebo and dapivirine vaginal rings. A. V. D. S. reports money from NIH. C. H. has received research support from Gilead Sciences managed through Johns Hopkins University, board membership to Population Council and UCLA. Consultancy fees from Viiv/GSK—past relationship, not active. Grants from NIH, Gates Foundation, and patents for IP not related to this paper. B. C. reports consultancy fees, travel expenses, and grants from Merck. I. M. is the Chief Medical Officer of AELIX Therapeutics and the Chief Scientific Officer of Orion Biotechnology has also received funding from Novicol Health Sciences and ABIVAX. All other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Funding Information: Funding. MTN-024/IPM 031 was conducted by the Microbicide Trials Network (MTN). MTN is funded by the National Institute of Allergy and Infectious Diseases under award numbers UM1AI068633, UM1AI068615, UM1AI106707, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the US National Institutes of Health. The vaginal rings used in this study were supplied by the IND sponsor, International Partnership for Microbicides (IPM). Publisher Copyright: {\textcopyright} The Author(s) 2018. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
month = mar,
day = "19",
doi = "10.1093/cid/ciy654",
language = "English (US)",
volume = "68",
pages = "1144--1151",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "7",
}