Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIVSF162p3viral kinetics and tenofovir pharmacokinetics when delivered via intravaginal rings

Background Intravaginal rings (IVR) for HIV prevention will likely be used by women on depot medroxyprogesterone acetate (DMPA) hormonal contraception. We used pigtailed macaques to evaluate the effects of DMPA on tenofovir disoproxil fumarate (TDF) IVR pharmacokinetics and viral shedding. Methods Mucosal tenofovir (TFV) levels were compared in SHIVSF162p3-negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIVSF162p3-positive DMPA-treated (n=6) and normally cycling (n=5) macaques. Results Similar median vaginal fluid TFV concentrations were observed in the DMPA-treated and cycling macaques over 4 weeks (1.2×105 and 1.1.×105 ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×107 and 8.15×104 copies/mL, respectively) and cycling macaques (3.98×107 and 1.47×103 copies/mL, respectively) were statistically similar. Conclusions DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding.