The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge

作者：Jessica Radzio, William R. Spreen, Yun Lan Yueh, James Michael Mitchell, Leecresia T. Jenkins, Jose Gerardo Garcia-Lerma, Walid Heneine · 发表于：Science Translational Medicine · 年份：2015 · DOI：10.1126/scitranslmed.3010297 · 被引用次数：78 · 研究领域：Adenosine and Purinergic Signaling、Infant Nutrition and Health、HIV/AIDS Research and Interventions

Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women.