Zhang Lanxin, Collins Simon, Fox Julie, von Kleist Max
Project group 5 "Systems Medicine of Infectious Disease", Robert-Koch Institute, Nordufer 20, Berlin, 13353, Germany.
HIV i-Base, London, UK.
J Int AIDS Soc. 2025 Jun;28 Suppl 1(Suppl 1):e26454. doi: 10.1002/jia2.26454.
Pre- and post-exposure prophylaxis (PrEP and PEP) are important pillars of the HIV prevention portfolio to reduce the risk of acquisition just before or after HIV exposure. While PrEP efficacy has been elucidated in many randomized clinical trials, corresponding data for PEP is extremely difficult to obtain in a controlled setting. Consequently, it is almost impossible to study the impact of PEP initiation delay and duration on HIV risk reduction clinically, which would inform recommendations on PEP use.
We employ pharmacokinetics, pharmacodynamics and viral dynamics models, along with individual factors, such as drug adherence to investigate the impact of initiation delay and PEP duration on HIV risk reduction. We evaluated PEP using two- and three-drug regimens with a TDF/FTC backbone. Moreover, we study PEP efficacy in the context of PrEP-to-PEP transitions.
In our simulations, early initiation of PEP emerged as a pivotal factor for HIV risk reduction. We found that 2-drug (TDF/FTC) PEP may insufficiently protect when initiated > 1 hour post-exposure. When adding a third drug, early initiation was still a critical factor; however, over 90% efficacy could be achieved when PEP was initiated 48 hours post-exposure and taken for at least 14-28 days, depending on the efficacy of the third-drug component. When investigating PrEP-PEP transitions, we observed that preceding PrEP can (1) contribute directly to prophylactic efficacy, and (2) boost subsequent PEP efficacy by delaying initial viral dynamics and building-up drug concentrations, overall facilitating self-managed transitioning between PrEP and PEP.
Our study confirms the critical role of early (< 48 hours) PEP initiation, preferably with three drugs taken for 28 days. Self-start with TDF/FTC and later addition of a third drug is better than not self-starting. Furthermore, our study highlights the synergy between recent PrEP intake and PEP and may help to inform recommendations on PEP use.
暴露前预防（PrEP）和暴露后预防（PEP）是预防艾滋病病毒（HIV）感染策略的重要组成部分，可降低在HIV暴露前后感染的风险。虽然PrEP的疗效已在许多随机临床试验中得到阐明，但在对照环境中极难获得PEP的相应数据。因此，几乎不可能在临床上研究PEP开始延迟和持续时间对降低HIV风险的影响，而这将为PEP的使用提供建议。
我们采用药代动力学、药效学和病毒动力学模型，以及个体因素，如药物依从性，来研究开始延迟和PEP持续时间对降低HIV风险的影响。我们使用以替诺福韦酯（TDF）/恩曲他滨（FTC）为基础的二联和三联疗法评估PEP。此外，我们在PrEP向PEP转换的背景下研究PEP的疗效。
在我们的模拟中，尽早开始PEP是降低HIV风险的关键因素。我们发现，暴露后超过1小时开始使用二联（TDF/FTC）PEP可能无法提供充分保护。添加第三种药物时，尽早开始仍然是关键因素；然而，根据第三种药物成分的疗效，暴露后48小时开始使用PEP并持续至少14至28天，可实现超过90%的疗效。在研究PrEP向PEP转换时，我们观察到先前的PrEP可以（1）直接提高预防效果，以及（2）通过延迟初始病毒动力学和积累药物浓度来提高后续PEP的疗效，总体上有助于PrEP和PEP之间的自我管理转换。
我们的研究证实了尽早（<48小时）开始使用PEP的关键作用，最好使用三联疗法并持续28天。自行开始使用TDF/FTC并随后添加第三种药物优于不自行开始。此外，我们的研究突出了近期PrEP使用与PEP之间的协同作用，可能有助于为PEP的使用提供建议。
