Laboratory Branch, CDC, Division of HIV/AIDS Prevention, MS G45, 1600 Clifton Road, Atlanta, GA 30329, USA.
J Virol. 2011 Aug;85(15):7933-6. doi: 10.1128/JVI.00843-11. Epub 2011 Jun 1.
Daily preexposure prophylaxis (PrEP) with Truvada (emtricitabine [FTC] and tenofovir disoproxil fumarate [TDF]) is a novel HIV prevention strategy recently found to reduce HIV incidence among men who have sex with men. We used a macaque model of HIV transmission to investigate if Truvada maintains prophylactic efficacy against an FTC-resistant isolate containing the M184V mutation. Five macaques received a dose of Truvada 3 days before exposing them rectally to the simian/human immunodeficiency virus mutant SHIV162p3(M184V), followed by a second dose 2 h after exposure. Five untreated animals were used as controls. Virus exposures were done weekly for up to 14 weeks. Despite the high (>100-fold) level of FTC resistance conferred by M184V, all five treated animals were protected from infection, while the five untreated macaques were infected (P = 0.0008). Our results show that Truvada maintains high prophylactic efficacy against an FTC-resistant isolate. Increased susceptibility to tenofovir due to M184V and other factors, including residual antiviral activity by FTC and/or reduced virus fitness due to M184V, may all have contributed to the observed protection.
每日暴露前预防（PrEP）用特鲁瓦达（恩曲他滨[FTC]和替诺福韦酯富马酸[TDF]）是一种新的 HIV 预防策略，最近被发现可降低男男性行为者的 HIV 感染率。我们使用猕猴 HIV 传播模型来研究特鲁瓦达是否对含有 M184V 突变的 FTC 耐药分离株保持预防功效。五头猕猴在直肠暴露于含有 M184V 突变的猿猴/人免疫缺陷病毒突变体 SHIV162p3（M184V）前 3 天接受特鲁瓦达剂量，暴露后 2 小时给予第二剂。五头未治疗的动物作为对照。每周进行病毒暴露，最多持续 14 周。尽管 M184V 赋予了高（>100 倍）的 FTC 耐药性，但所有五头接受治疗的动物都免受感染，而五头未接受治疗的猕猴均被感染（P=0.0008）。我们的结果表明，特鲁瓦达对 FTC 耐药分离株保持高度的预防功效。M184V 以及其他因素（包括 FTC 的残留抗病毒活性和/或由于 M184V 导致的病毒适应性降低）导致对替诺福韦的敏感性增加，可能都促成了观察到的保护作用。
