1Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Clin Pharmacol Ther. 2018 Dec;104(6):1082-1097. doi: 10.1002/cpt.1227. Epub 2018 Nov 1.
The US Food and Drug Administration (FDA) approved oral daily tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis of human immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized controlled trials (RCTs), one in men who have sex with men (MSM) and another in HIV serodiscordant heterosexual couples. Subsequently, even greater efficacy has been demonstrated in MSM with rapid population-level incidence reductions in some locations. In contrast, studies of antiretroviral pre-exposure prophylaxis (PrEP) in heterosexual women showed only modest or no efficacy, largely attributed to low adherence. The mixed results of antiretroviral-based PrEP bear witness to unique drug development challenges at this complicated intersection of sexual behavior, public health, and drug development. Multiple innovative methods and formulation strategies followed to address unmet medical needs of persons struggling with daily oral PrEP adherence or preference for nonsystemic PrEP options. Clinical pharmacology plays essential roles throughout this PrEP development process, especially in early product development and through pharmacologically informed enhancement and interpretation of clinical trials.
美国食品和药物管理局（FDA）基于两项随机对照试验（RCT）于 2012 年批准每日口服替诺福韦/恩曲他滨（Truvada）用于人类免疫缺陷病毒（HIV）感染的暴露前预防。其中一项试验针对男男性行为者（MSM），另一项则针对 HIV 血清不一致的异性恋夫妇。随后，在 MSM 中观察到了更高的疗效，在一些地方迅速降低了人群感染率。相比之下，在异性恋女性中进行的抗逆转录病毒暴露前预防（PrEP）研究仅显示出适度或无疗效，这主要归因于低依从性。抗逆转录病毒 PrEP 的混合结果证明了在性行为、公共卫生和药物开发这一复杂交叉点上存在独特的药物开发挑战。为了解决每天口服 PrEP 依从性或对非系统性 PrEP 选择的偏好方面存在的未满足的医疗需求，随后采用了多种创新方法和配方策略。临床药理学在整个 PrEP 开发过程中都发挥着至关重要的作用，尤其是在早期产品开发以及通过药理学知识增强和解释临床试验方面。
