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

Jessica Radzio, William Spreen, Yun Lan Yueh, James Mitchell, Leecresia Jenkins, J. Gerardo García-Lerma, Walid Heneine

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Abstract

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 inmacaques. Female pigtailmacaques (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 achievablewith 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.

Original languageEnglish (US)
Article number270ra5
JournalScience Translational Medicine
Volume7
Issue number270
DOIs
StatePublished - Jan 14 2015

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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