Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices.

BACKGROUND: Increasing evidence suggests that depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with an increased risk of HIV infection; however the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital mucosal proteome and microbiome to gain mechanistic insights. METHODS: Cervicovaginal secretions from 86 Kenyan women including self-reported DMPA (n=23) and non-hormonal contraceptive users (n=63) and women who practice vaginal drying (n=46) were analyzed using tandem-mass spectrometry in a cross sectional manner. RESULTS: We identified 473 human and 486 bacterial proteins from 18 different genera. DMPA use associated with increased hemoglobin and immune activation (HBD HBB ALAD IL36G) and decreased epithelial repair proteins (TFF3 F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1 MYH9 PLAUR PADI4). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. Vaginal drying associated with more diverse (H-index: 0.71 vs 0.45 p=0.0089) bacterial communities containing Gardnerella vaginalis whereas DMPA showed no significant changes in community composition or diversity. CONCLUSIONS: These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers and future investigations are needed to confirm their relationship with HIV risk in women. (c) The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.