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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. [ABSTRACT FROM AUTHOR]

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 (1.2×10 5 and 1.1.×10 5  ng/mL, respectively). Median plasma viremia and vaginal shedding AUC of the DMPA-treated (2.73×10 7 and 8.15×10 4 copies/mL, respectively) and cycling macaques (3.98×10 7 and 1.47×10 3 copies/mL, respectively) were statistically similar., Conclusions: DMPA does not affect TDF IVR pharmacokinetics or SHIV shedding., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate-treated macaques or repeated viral challenges in cycling macaques. We tested the efficacy of an intravaginal tenofovir disoproxil fumarate (TDF) ring in a model combining repeated 30-mg injections of depot medroxyprogesterone acetate every 6 weeks with vaginal viral challenges weekly for 12 weeks. Twelve macaques were randomized to TDF or placebo rings. All placebo macaques became infected after a median of 2 exposures, whereas only 1 TDF macaque became infected at the eighth exposure (P = 0.0012). The TDF ring provides durable protection in a stringent challenge model.