Influence of dapivirine vaginal ring use on cervicovaginal immunity and functional microbiome in adolescent girls

TitleInfluence of dapivirine vaginal ring use on cervicovaginal immunity and functional microbiome in adolescent girls
Publication TypePublication
Year of Publication2021
AuthorsZuend CFarr, Noël-Romas L, Hoger S, McCorriser S, Westmacott G, Marrazzo J, Hillier SL, Dezzutti C, Squires K, Bunge KE, Burgener A
JournalAIDS
Volume35
Issue3
Pagination369-380
Date Published2021 03 01
ISSN1473-5571
KeywordsAdolescent, Anti-HIV Agents, Contraceptive Devices, Female, Female, HIV Infections, Humans, Lactobacillus, Microbiota, Pyrimidines, Vagina
Abstract

<p><b>OBJECTIVE: </b>The antiretroviral-based dapivirine vaginal ring reduced HIV risk among women in phase III clinical trials. However, limited data exists on the impact of dapivirine on the vaginal microenvironment in adolescents.</p><p><b>DESIGN: </b>A comprehensive metaproteomics approach was used to assess host proteome and microbiome changes in cervicovaginal mucus with dapivirine ring use in adolescents enrolled in the MTN-023/IPM 030 (MTN-023) trial.</p><p><b>METHODS: </b>Participants were randomized 3 : 1 to use dapivirine or placebo vaginal rings monthly for 6 months. Cervicovaginal samples from a subset of 35 participants (8 placebo, 27 dapivirine) were analyzed.</p><p><b>RESULTS: </b>Mass spectrometry analysis identified 405 human and 2467 bacterial proteins belonging to 15 unique genera. The host proteome belonged to many functional pathways primarily related to inflammation. When stratified by study treatment arm, 18 (4.4%) and 28 (6.9%) human proteins were differentially abundant (adjusted P < 0.05) between baseline and follow-up in the placebo and dapivirine arms, respectively. The vaginal microbiome was predominantly composed of Lactobacillus, Gardnerella, and Prevotella. Although bacterial taxa did not differ by arm or change significantly, Lactobacillus crispatus increased (P < 0.001) and Lactobacillus iners decreased (P < 0.001) during the 6-month follow-up. There were no significant differences in bacterial functions by arm or time in the trial. Protected vaginal sex significantly associated with decreased neutrophil inflammatory biomarkers and may be associated with changes in bacterial taxa and metabolism.</p><p><b>CONCLUSION: </b>Condom use may associate with differences to inflammation and bacterial function but dapivirine ring use does not, thereby supporting the mucosal safety profile of this vaginal ring for adolescents.</p>

DOI10.1097/QAD.0000000000002751
Alternate JournalAIDS
PubMed ID33181534
PubMed Central IDPMC7924934
Grant ListU01 HD040533 / HD / NICHD NIH HHS / United States
UM1 AI068615 / AI / NIAID NIH HHS / United States
UM1 AI068633 / AI / NIAID NIH HHS / United States
UM1 AI106707 / AI / NIAID NIH HHS / United States