Effect of Hormonal Contraception on Pharmacokinetics of Vaginal Tenofovir in Healthy Women: Increased Tenofovir Diphosphate in Injectable Depot Medroxyprogesterone Acetate Users

OBJECTIVE: Endogenous and exogenous contraceptive hormones may affect mucosal pharmacokinetics (PKs) of topical antiretrovirals such as tenofovir. We present PK data from healthy women using tenofovir vaginal gel, at baseline (follicular and luteal phases) and after oral contraceptive pill (OCP) or depot medroxyprogesterone acetate (DMPA) use. METHODS: CONRAD A10-114 was a prospective, interventional, open-label, parallel study. We enrolled 74 women and 60 completed the study (32 and 28 who selected OCPs or DMPA, respectively). Participants used 2 doses of tenofovir gel separated by 2 hours, without intercourse, and were examined 3 or 11 hours after the last dose. We assessed pharmacokinetics in plasma, cervicovaginal (CV) aspirate, and vaginal tissue. RESULTS: In general, there were no significant differences in mucosal tenofovir and tenofovir diphosphate concentrations (P > 0.23) in the follicular and luteal phases, except for lower mean tenofovir tissue concentrations (P 10 ng/mL). Mean tissue tenofovir diphosphate increased to 6229 fmol/mg after DMPA use compared with 3693 and 1460 fmol/mg in the follicular and luteal phases, respectively (P 1.00 ng/mL in CV aspirate and tenofovir diphosphate >1000 fmol/mg).