Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC 27599-7569, USA.
J Acquir Immune Defic Syndr. 2013 Jul;63 Suppl 2(0 2):S240-7. doi: 10.1097/QAI.0b013e3182986ff8.
Strategies to prevent HIV infection using preexposure prophylaxis are required to curtail the HIV pandemic. The mucosal tissues of the genital and rectal tracts play a critical role in HIV acquisition, but antiretroviral (ARV) disposition and correlates of efficacy within these tissues are not well understood. Preclinical and clinical strategies to describe ARV pharmacokinetic-pharmacodynamic relationships within mucosal tissues are currently being investigated. In this review, we summarize the physicochemical and biologic factors influencing ARV tissue exposure. Furthermore, we discuss the necessary steps to generate relevant pharmacokinetic-pharmacodynamic data and the challenges associated with this process. Finally, we suggest how preclinical and clinical data might be practically translated into optimal preexposure prophylaxis dosing strategies for clinical trials testing using mathematical modeling and simulation.
需要使用暴露前预防策略来预防 HIV 感染，以遏制 HIV 大流行。生殖器和直肠黏膜组织在 HIV 感染中起着关键作用，但这些组织中抗逆转录病毒 (ARV) 的处置和疗效相关因素尚不清楚。目前正在研究描述 ARV 在黏膜组织中药代动力学-药效学关系的临床前和临床策略。在这篇综述中，我们总结了影响 ARV 组织暴露的理化和生物学因素。此外，我们还讨论了生成相关药代动力学-药效学数据的必要步骤，以及与该过程相关的挑战。最后，我们建议如何通过数学建模和模拟，将临床前和临床数据实际转化为最佳的暴露前预防给药策略，用于临床试验测试。
