Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
AIDS Res Hum Retroviruses. 2022 Dec;38(12):909-923. doi: 10.1089/AID.2022.0057. Epub 2022 Oct 25.
The HIV epidemic remains a significant public health burden. Women represent half of the global HIV epidemic, yet there is an urgent need for a variety of prevention options to meet the needs of more women. Pre-exposure prophylaxis (PrEP) is a valuable prevention tool that uses antiretrovirals before a potential HIV exposure to prevent virus transmission. Development of effective preventive drug regimens for women is dependent on convenient dosing schedules and routes of administration, and on identifying defined target concentrations in mucosal tissues that provide complete protection against HIV transmission. There is a critical need for a translational model that can accurately predict target concentrations that are completely protective against HIV infection. There is no gold-standard preclinical model to predict PrEP efficacy. In this study, we review the strengths and limitations of three different preclinical models and their utility in predicting target concentrations in the female genital tract: humanized mice, non-human primates, and the tissue model.
艾滋病病毒流行仍然是一个重大的公共卫生负担。妇女占全球艾滋病病毒流行的一半，但迫切需要各种预防选择来满足更多妇女的需求。暴露前预防（PrEP）是一种有价值的预防工具，它在可能接触艾滋病毒之前使用抗逆转录病毒药物来预防病毒传播。为妇女开发有效的预防药物方案取决于方便的剂量方案和给药途径，以及确定在粘膜组织中提供完全预防艾滋病毒传播的定义靶浓度。迫切需要一种能够准确预测完全预防艾滋病毒感染的靶浓度的转化模型。目前还没有预测 PrEP 疗效的金标准临床前模型。在这项研究中，我们回顾了三种不同的临床前模型的优缺点及其在预测女性生殖道靶浓度方面的应用：人源化小鼠、非人类灵长类动物和组织模型。
