Tenofovir disoproxil fumarate intravaginal ring protects high-dose depot medroxyprogesterone acetate-treated macaques from multiple SHIV exposures.

Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate (DMPA)-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 DMPA 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 one TDF macaque became infected at the eighth exposure (p=0.0012). The TDF ring provides durable protection in a stringent challenge model.