Reproductive age women may choose to concurrently use topical antiretrovirals and hormonal
contraceptives (HCs) to simultaneously prevent 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 cervicovaginal (CV) mucosal data from healthy women before and after initiation of either
oral contraceptive pills (OCPs) or depot
medroxyprogesterone acetate (
DMPA) injection. 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 and
DMPA, respectively). Participants provided CV lavage, vaginal biopsies, and CV swabs at baseline in the luteal phase and then ∼6 weeks after initiating HCs. 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, whereas for
DMPA users, they were distributed throughout the vaginal tissue, including the epithelium (CD45+, CD3+, CD4+, and CD1a+).
Contraceptive use altered concentrations of soluble CV inflammatory and immune mediators, with significant reductions in some proinflammatory
cytokines and
secretory leukoprotease inhibitor. Compared with baseline, p24
antigen production after ex vivo HIV-1
infection of vaginal biopsies doubled after
DMPA use, but all p-values were >.05. HIV-1 replication was significantly higher in
DMPA-exposed tissues compared with those from the OCP group at the end of the tissue culture (p = .01). Although not statistically significant, median in vitro inhibition of HIV-1 by CV fluid (innate
antiviral activity), was reduced by ∼50% with HCs (p > .21). Exposure to exogenous
contraceptive hormones significantly increased vaginal immune cells and reduced CV proinflammatory
cytokines and
antimicrobial peptides.
DMPA users showed higher susceptibility to HIV-1 ex vivo
infection.