InChI | InChI=1S/C19H17F2N3O5/c1-9-8-29-14-7-23-6-12(16(25)17(26)15(23)19(28)24(9)14)18(27)22-5-10-2-3-11(20)4-13(10)21/h2-4,6,9,14,26H,5,7-8H2,1H3,(H,22,27)/t9-,14+/m0/s1 |
Reference | 1. Sci Transl Med. 2015 Jan 14;7(270):270ra5. doi: 10.1126/scitranslmed.3010297.<br />
The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.<br />
Radzio J(1), Spreen W(2), Yueh YL(2), Mitchell J(1), Jenkins L(1), García-Lerma JG(3), Heneine W(1).<br />
Author information:<br />
(1)Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. (2)GlaxoSmithKline, Research Triangle Park, NC 27709, USA. (3)Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA. [email protected].<br />
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.
|