Ortblad Katrina F, Brown Elizabeth R, Heffron Renee, Ngure Kenneth, Mujugira Andrew, Donnell Deborah
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
J Int AIDS Soc. 2025 Jun;28 Suppl 1(Suppl 1):e26475. doi: 10.1002/jia2.26475.
New longer-acting antiretroviral (ARV) drugs-that is single doses with antiviral activity for at least a month-are being utilized for HIV treatment and pre-exposure prophylaxis (PrEP) but have not been explored for post-exposure prophylaxis (PEP). A "one-and-done" simplification of PEP has the potential to serve the HIV prevention needs of individuals not being met with traditional services and expand overall biomedical HIV prevention coverage. We discuss challenges with the assessment of PEP effectiveness in human trials and potential study designs that could generate evidence needed to inform the use of new, single-administered, long-acting ARVs for PEP.
Challenges with determining the effectiveness of new long-acting PEP agents in human trials include the low likelihood of observing an HIV acquisition and the short period for outcome assessment (likely 1 month) following PEP administration. Additional challenges include recruiting individuals in the brief window in which they could benefit (<72 hours of a potential HIV exposure) and ethics of conducting informed consent during a period of high stress/vulnerability. Consequently, design approaches where the efficacy goal is to establish that the HIV incidence rate following PEP administration (of the standard or a novel agent) approaches zero should be considered. HIV RNA testing conducted within 5 days of a potential exposure could define prevention per exposure. Novel recruitment venues-such as community-based retail or online pharmacies-could be used to reach individuals after a potential exposure. Potential study designs include one- or two-arm individual-level product assignment aimed at demonstration of short-course efficacy or longer-term effectiveness compared to a background rate; cluster-randomized controlled trials of recruitment venues; and novel individual-level approaches that either do not or do utilize randomization in combination with choice, enabling assessment of preferences and effectiveness.
Over the past decade, multiple new HIV PrEP products-but no new PEP products-have been developed to meet the diverse needs of individuals seeking HIV prevention services. Challenges exist with generating PEP effectiveness evidence, but they are not insurmountable. Effectiveness research on new PEP products could advance the number of HIV prevention options available.
新型长效抗逆转录病毒（ARV）药物，即单剂量具有至少一个月抗病毒活性的药物，正被用于艾滋病治疗和暴露前预防（PrEP），但尚未用于暴露后预防（PEP）。将PEP简化为“一剂了事”有可能满足传统服务未能满足的个体的艾滋病预防需求，并扩大生物医学艾滋病预防的总体覆盖范围。我们讨论了在人体试验中评估PEP有效性所面临的挑战以及潜在的研究设计，这些设计可能会产生为将新型单剂量长效ARV药物用于PEP提供依据所需的证据。
在人体试验中确定新型长效PEP药物有效性所面临的挑战包括观察到艾滋病病毒感染的可能性较低以及在PEP给药后进行结果评估的时间较短（可能为1个月）。其他挑战包括在个体可能受益的短暂窗口期（潜在艾滋病病毒暴露后<72小时）招募个体，以及在高压力/易受伤害期间进行知情同意的伦理问题。因此，应考虑采用这样的设计方法，即疗效目标是确定PEP给药后（标准药物或新型药物）的艾滋病病毒发病率接近零。在潜在暴露后5天内进行的艾滋病病毒RNA检测可以确定每次暴露的预防效果。新型招募场所，如社区零售药店或网上药店，可用于在潜在暴露后接触个体。潜在的研究设计包括单臂或双臂个体水平的产品分配，旨在证明与背景率相比的短期疗效或长期有效性；招募场所的整群随机对照试验；以及新型个体水平方法，这些方法要么不使用随机化，要么将随机化与选择相结合，从而能够评估偏好和有效性。
在过去十年中，已开发出多种新型艾滋病病毒PrEP产品，但没有新型PEP产品，以满足寻求艾滋病预防服务的个体的多样化需求。在生成PEP有效性证据方面存在挑战，但并非无法克服。对新型PEP产品的有效性研究可能会增加可用的艾滋病预防选择数量。
