Cottrell Mackenzie L, Kashuba Angela D M
University of North Carolina at Chapel Hill, UNC Eshelman School of Pharmacy, Chapel Hill, NC, USA.
J Clin Pharmacol. 2014 Jun;54(6):603-15. doi: 10.1002/jcph.292. Epub 2014 Mar 28.
Worldwide, HIV disproportionately affects women who are often unable to negotiate traditional HIV preventive strategies such as condoms. In the absence of an effective vaccine or cure, chemoprophylaxis may be a valuable self-initiated alternative. Topical microbicides have been investigated as one such option. The first generation topical microbicides were non-specific, broad-spectrum antimicrobial agents, including surfactants, polyanions, and acid buffering gels, that generally exhibited contraceptive properties. After extensive clinical study, none prevented HIV infection, and their development was abandoned. Second generation topical microbicides include agents with selective mechanisms of antiviral activity. Most are currently being used for, or have previously been explored as, drugs for treatment of HIV. The most advanced of these is tenofovir 1% gel: the first topical agent shown to significantly reduce HIV infection by 39% compared to placebo. This review summarizes the evolution of topical microbicides for HIV chemoprophylaxis, highlights important concepts learned, and offers current and future considerations for this area of research.
在全球范围内，艾滋病毒对女性的影响尤为严重，她们往往无法就使用避孕套等传统的艾滋病毒预防策略进行协商。在缺乏有效疫苗或治愈方法的情况下，化学预防可能是一种有价值的自我启动的替代方法。局部用杀微生物剂已作为一种选择进行了研究。第一代局部用杀微生物剂是非特异性的广谱抗菌剂，包括表面活性剂、聚阴离子和酸缓冲凝胶，通常具有避孕特性。经过广泛的临床研究，没有一种能预防艾滋病毒感染，因此它们的研发被放弃。第二代局部用杀微生物剂包括具有选择性抗病毒活性机制的药物。目前大多数正在用于或以前曾被探索作为治疗艾滋病毒的药物。其中最先进的是1%替诺福韦凝胶：与安慰剂相比，第一种局部用药显示能将艾滋病毒感染显著降低39%。本综述总结了用于艾滋病毒化学预防的局部用杀微生物剂的演变，强调了所学的重要概念，并为该研究领域提供了当前和未来的考虑因素。
