A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge

摘要: Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in low-dose intrarectal SHIV (simian-human rhesus macaque challenge model. We examined pharmacokinetics efficacy GSK744 LA as PrEP against repeat high-dose intravaginal female macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated were dosed (50 mg/kg) monthly, systemic tissue drug concentrations lower than previously observed male macaques. fivefold on average cervical tissues rectal tissues. Eight at week 0, four served controls. All animals received SHIV162P3 1. No infection detected LA-treated macaques, whereas viremia 1 2 weeks after all control animals. The given second administration 4 further challenged 5 7. treatment protected six eight three challenges, became infected first (P = 0.0003, log-rank test). These results support clinical development for PrEP.