TY - JOUR
T1 - The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge
AU - Radzio, Jessica
AU - Spreen, William
AU - Yueh, Yun Lan
AU - Mitchell, James
AU - Jenkins, Leecresia
AU - García-Lerma, J. Gerardo
AU - Heneine, Walid
N1 - Publisher Copyright:
© 2015, American Association for the Advancement of Science. All rights reserved.
PY - 2015/1/14
Y1 - 2015/1/14
N2 - 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.
AB - 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.
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U2 - 10.1126/scitranslmed.3010297
DO - 10.1126/scitranslmed.3010297
M3 - Article
C2 - 25589631
AN - SCOPUS:84921044609
SN - 1946-6234
VL - 7
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 270
M1 - 270ra5
ER -