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 in vivo 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 ex vivo tissue model.

中文翻译：

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预测女性暴露前预防目标浓度的转化模型


艾滋病毒流行仍然是一个重大的公共卫生负担。女性占全球艾滋病毒流行的一半，但迫切需要多种预防方案来满足更多女性的需求。暴露前预防 (PrEP) 是一种有价值的预防工具，可在潜在的 HIV 暴露之前使用抗逆转录病毒药物来预防病毒传播。为女性开发有效的预防药物方案取决于方便的给药方案和给药途径，以及确定粘膜组织中明确的目标浓度，以提供全面的预防艾滋病毒传播的保护。迫切需要一种能够准确预测完全预防 HIV 感染的体内目标浓度的转化模型。没有金标准的临床前模型来预测 PrEP 疗效。在这项研究中，我们回顾了三种不同临床前模型的优点和局限性及其在预测女性生殖道目标浓度方面的效用：人源化小鼠、非人灵长类动物和离体组织模型。