Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Cold Spring Harb Perspect Med. 2012 Mar;2(3):a007419. doi: 10.1101/cshperspect.a007419.
The impressive advances in antiretroviral (ARV) therapy of chronic human immunodeficiency virus (HIV) infections during the last decade and the availability of potent ARV drugs have fueled interest in using chemoprophylaxis as a novel HIV prevention strategy. Preexposure prophylaxis (PrEP) refers to the use of ARV drugs in HIV-negative persons to prevent HIV infection. The rationale for PrEP builds on the success of ARV prophylaxis in preventing mother-to-child transmission of HIV and on a large body of animal studies that show the efficacy of PrEP against mucosal and parenteral infection. We focus on oral administration of ARV drugs for prevention of HIV infection. Identifying an effective prophylactic pill that individuals can take outside the setting of sexual intercourse precludes the necessity to disclose such use to their partners, thereby empowering those who might not be in a position to negotiate with their partners. Several human clinical trials evaluating the efficacy of daily regimens of the HIV reverse-transcriptase (RT) inhibitors tenofovir disoproxil fumarate (TDF) or Truvada (TDF and emtricitabine [FTC]) are under way among high-risk populations. The results of one trial among men who have sex with men showed that daily Truvada was safe and effective, providing the first support for oral PrEP as a prevention strategy. Here we outline the preclinical and clinical research on oral PrEP, pharmacologic considerations, and future directions and challenges.
在过去十年中，抗逆转录病毒（ARV）疗法在慢性人类免疫缺陷病毒（HIV）感染方面取得了令人瞩目的进展，并且有了有效的 ARV 药物，这激发了人们对将化学预防作为一种新的 HIV 预防策略的兴趣。暴露前预防（PrEP）是指在 HIV 阴性者中使用 ARV 药物来预防 HIV 感染。PrEP 的原理是基于 ARV 预防在预防母婴传播 HIV 方面的成功，以及大量动物研究表明 PrEP 对粘膜和肠外感染的有效性。我们专注于 ARV 药物的口服给药以预防 HIV 感染。确定一种有效的预防性药丸，个体可以在性行为之外服用，这就排除了向其伴侣披露此类使用的必要性，从而赋予那些可能无法与其伴侣协商的人权力。正在高危人群中进行几项评估每日 HIV 逆转录酶（RT）抑制剂替诺福韦二吡呋酯（TDF）或特鲁瓦达（TDF 和恩曲他滨[FTC]）的每日方案疗效的人类临床试验。一项针对男男性行为者的试验结果表明，每日服用特鲁瓦达是安全有效的，首次支持将口服 PrEP 作为一种预防策略。在这里，我们概述了口服 PrEP 的临床前和临床研究、药理学考虑因素以及未来的方向和挑战。
