Pharmacokinetic and pharmacodynamic impacts of depot medroxyprogesterone acetate use on HIV pre-exposure prophylaxis in women.

BACKGROUND Depot medroxyprogesterone acetate (DMPA) is a commonly used contraceptive in areas where use of tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis (PrEP) is increasing. OBJECTIVES We aimed to investigate the impact of DMPA on PrEP drug pharmacokinetics and pharmacodynamics in women using PrEP before and after DMPA administration. METHODS In this pilot study, twelve HIV-negative women ages 18-45 underwent biological sample collection at three time points: before study drug, after 2 weeks of daily PrEP use alone, and after 2 weeks of daily PrEP and concomitant DMPA use. We measured drug and drug metabolites in plasma, peripheral blood mononuclear cells, cervicovaginal fluid, cervical tissue, and rectal fluid after each 2-week course of PrEP. We measured HIV replication ex vivo in genital tissue biopsies and innate anti-HIV activity in cervicovaginal fluid before PrEP and after both courses. We compared drug concentrations after PrEP alone to after PrEP and DMPA in the same participant using Wilcoxon signed-rank tests. We used mixed effects linear regression models to compare pharmacodynamic measures for each participant at pre-drug baseline, after PrEP alone, and after PrEP and DMPA. RESULTS We found no significant differences in PrEP drug and drug metabolite concentrations in any compartment during concomitant DMPA use compared to use of PrEP alone, except for a reduction in emtricitabine concentration in cervical tissue. We found no difference in HIV replication in cervical tissue or anti-HIV activity in cervicovaginal fluid during concomitant DMPA and PrEP use compared to during PrEP use alone. CONCLUSIONS Concomitant use of DMPA does not clinically alter pharmacokinetics or pharmacodynamics of PrEP in women. These data support the safety of DMPA use in women using PrEP.