The Effect of Hormonal Contraception on Cervico-Vaginal Mucosal Endpoints associated with Human Immunodeficiency Virus Acquisition.

OBJECTIVE: Reproductive age women may choose to concurrently use topical anti-retrovirals (ARVs) and hormonal contraceptives (HC) to simultaneously prevent human immunodeficiency virus type 1 (HIV-1) infection and unintended/mistimed pregnancy. There are conflicting data on the effect of HCs on mucosal susceptibility to HIV-1. The objective of this study was to evaluate cervico-vaginal (CV) mucosal data from healthy women before and after initiation of either oral contraceptive pills (OCPs) or depot medroxyprogesterone acetate injection (DMPA).

METHODS: CONRAD A10-114 was a prospective, open-label, parallel cohort study. We enrolled 74 women and 62 completed the visits (32 and 30 who selected OCPs or DMPA, respectively). Participants provided CV lavage, vaginal biopsies and CV swabs at baseline in the luteal phase and then approximately 6 weeks after initiating HCs.

RESULTS: After contraceptive initiation, there were significant increases in vaginal immune cell density among both DMPA and OCP users. Changes for OCP users were concentrated in the subepithelial lamina propria, while, for DMPA users, they were distributed throughout the vaginal tissue, including the epithelium (CD45+, CD3+, CD4+, CD1a+). Contraceptive use altered concentrations of soluble CV inflammatory and immune mediators, with significant reductions in some proinflammatory cytokines and secretory leukoprotease inhibitor (SLPI). Compared to baseline, p24 antigen production after ex vivo HIV-1 infection of vaginal biopsies doubled after DMPA use, but all p values were > 0.05. HIV-1 replication was significantly higher in DMPA exposed tissues compared to those from the OCP group at the end of the tissue culture (p=0.01). Although not statistically significant, median in vitro inhibition of HIV-1 by CV fluid (innate antiviral activity), was reduced by approximately 50% with HCs (p values >0.21).

CONCLUSIONS: Exposure to exogenous contraceptive hormones significantly increased vaginal immune cells and reduced CV pro-inflammatory cytokines and anti-microbial peptides. DMPA users showed higher susceptibility to HIV-1 ex vivo infection.