Vaginal Microbiota and Cytokines Among Pregnant and Breastfeeding Women in Clinical Trials of the Dapivirine Vaginal Ring and Oral Tenofovir Disoproxil Fumarate/Emtricitabine

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Abstract Background Vaginal dysbiosis is associated with HIV acquisition and preterm delivery. Our objective was to evaluate prevalent vaginal infections, and changes in microbiota and cytokines among pregnant and breastfeeding women from 4 African countries using dapivirine vaginal ring (DVR) or oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 2 parallel nonoverlapping trials. Methods MTN-042 (NCT03965923) was a randomized trial evaluating daily TDF/FTC or monthly DVR during pregnancy (n = 558), and MTN-043 (NCT04140266) was a randomized study evaluating TDF/FTC or DVR during breastfeeding (n = 197). Women were evaluated for vaginal infections at enrollment and follow-up using Nugent score and BD Max™ Vaginal Panel. Microbiota was evaluated by quantitative PCR for 12 bacterial targets; 5 cytokines and RANTES were evaluated by MAGPIX. Rates of change in vaginal microbiota and cytokines and prevalence of vaginal infections were evaluated using generalized linear mixed models and Benjamini–Hochberg (BH)-adjusted P values. Results Vaginal infections, microbiota and cytokines did not differ between the 2 study arms at baseline. Lactobacillus crispatus was less frequently detected postpartum and during breastfeeding compared with pregnancy. Bacterial vaginosis (BV) and Candida were common during pregnancy and breastfeeding, but there was no significant difference in the rate of change in these infections by study arm. BV-associated microbiota and cytokines changed over pregnancy and postpartum, but the rate of change by study arm did not differ. Conclusions Vaginal infections, microbiota or cytokines/chemokines changes were similar in women using DVR or TDF/FTC. These data augment the robust safety profile for DVR to support its use during pregnancy and breastfeeding.