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

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Science Translational Medicine  14 Jan 2015:
Vol. 7, Issue 270, pp. 270ra5
DOI: 10.1126/scitranslmed.3010297

A Step-Up for PrEP

Daily preexposure prophylaxis (PrEP) is effective in preventing HIV acquisition among men and women, but many are not able to adhere to the daily pill schedule and cannot fully benefit from PrEP. New long-acting antiretroviral formulations provide sustained drug delivery for many weeks and do not require adherence between medication visits. Here, Radzio et al. showed in macaques that the long-acting integrase inhibitor GSK744, at concentrations achievable in humans by quarterly injections, afforded protection against repeated vaginal simian HIV challenges. These findings support the clinical development of GSK744 LA as a PrEP agent for HIV prevention in women.


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.

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