Repeated administration of high-dose depot medroxyprogesterone acetate does not alter SHIV_{SF 162p3} viral 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 SHIV_{SF 162p3}-negative DMPA-treated (n=4) and normally cycling (n=6) macaques receiving TDF IVRs. Plasma viremia and vaginal shedding were determined in groups of SHIV_{SF 162p3}-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.