Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA.
Trends Pharmacol Sci. 2010 Feb;31(2):74-81. doi: 10.1016/j.tips.2009.10.009. Epub 2009 Dec 4.
In the absence of an effective vaccine, HIV continues to spread worldwide, emphasizing the need for new biomedical interventions to limit its transmission. Appreciation of the challenges that HIV has to face to initiate an infection mucosally has spurred interest in evaluating the use of antiretroviral drugs to prevent infection. Recent animal studies using macaques or humanized mice models of mucosal transmission of SIV or HIV have shown that daily or intermittent pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) can exploit early virus vulnerabilities and effectively prevent establishment of infection. These preclinical findings have fueled interest in evaluating the safety and efficacy of PrEP in humans. We provide an overview of the rationale behind PrEP and discuss the next steps in PrEP research, including the need to better define the ability of current drugs to reach and accumulate in mucosal tissues and protect cells that are primary targets during early HIV infection.
在缺乏有效疫苗的情况下,艾滋病毒继续在全球范围内传播,这强调了需要新的生物医学干预措施来限制其传播。对艾滋病毒在黏膜感染中所面临的挑战的认识,激发了人们评估使用抗逆转录病毒药物来预防感染的兴趣。最近使用猕猴或人源化小鼠模型进行的动物研究表明,每天或间歇性地使用富马酸替诺福韦二吡呋酯(TDF)和恩曲他滨(FTC)进行暴露前预防(PrEP)可以利用早期病毒的弱点,有效地预防感染的建立。这些临床前研究结果激发了人们对评估 PrEP 在人类中的安全性和有效性的兴趣。我们提供了 PrEP 的基本原理概述,并讨论了 PrEP 研究的下一步步骤,包括需要更好地定义当前药物在到达和积累黏膜组织以及保护在早期 HIV 感染中成为主要靶标的细胞方面的能力。