Parikh Urvi M, Jacobs Jana L, Njuguna Njambi, Torjesen Kristine, Mellors John W
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
FHI 360 Kenya, Nairobi, Kenya.
J Int AIDS Soc. 2025 Jul;28 Suppl 2(Suppl 2):e26491. doi: 10.1002/jia2.26491.
Multiple effective antiretroviral-based pre-exposure prophylaxis (PrEP) modalities for HIV-1 prevention are now available or under investigation but their safe rollout requires implementable HIV-1 testing strategies that accurately identify rare cases of HIV-1 acquisition. Current PrEP testing guidelines and testing algorithms in PrEP studies are varied, using single or combinations of rapid antibody-based diagnostic testing, qualitative or quantitative nucleic acid testing, and/or sample collection for retrospective analyses with sensitive research assays for HIV-1 nucleic acid detection. The objective of this commentary is to summarize current and alternative HIV testing approaches for PrEP implementation to guide best practices for individual programmes.
Diagnosing HIV-1 in PrEP users is challenging because (1) rarity of breakthrough HIV-1 in individuals on PrEP that increases the risk of a false-positive test; (2) modification of acute HIV infection by PrEP; and (3) PrEP delivery in community settings with inadequate testing infrastructure. Current best practices indicate the use of rapid diagnostic tests or self-testing as recommended by national testing algorithms and the World Health Organization (WHO). The use of nucleic acid testing such as plasma HIV-1 RNA polymerase chain reaction may allow earlier detection of HIV-1 but feasibility and risk of false positive are downsides. Sensitive tests to detect single-copy HIV-1 RNA in plasma and integrated proviral DNA in blood mononuclear cells may be important methods to resolve ambiguous HIV-1 diagnosis in research settings. Delayed diagnoses could lead to drug resistance emergence under long-acting PrEP selection, whereas single unconfirmed false-positive tests could create diagnostic challenges in users of long-acting PrEP. The cost, feasibility and positive predictive value of HIV tests are important considerations for PrEP programmes.
Optimal strategies to detect HIV-1 acquisition among users of different PrEP modalities are evolving. While new guidance from the WHO recommends HIV-1 testing by serological assays or self-testing with PrEP use, feasible plans for clinical management of rare cases of breakthrough on PrEP and ambiguous diagnoses are still needed. The data from PrEP studies and scale-up will help us assess the value of different tests and testing approaches for their inclusion in HIV detection algorithms across PrEP modalities.
目前已有多种基于高效抗逆转录病毒药物的暴露前预防（PrEP）方案可用于预防HIV-1感染，还有一些方案正在研究中。但要安全推广这些方案，需要有可行的HIV-1检测策略，以准确识别罕见的HIV-1感染病例。目前PrEP研究中的检测指南和检测算法各不相同，采用了基于快速抗体的诊断检测、定性或定量核酸检测的单一方法或组合方法，和/或采集样本用于回顾性分析，并采用敏感的HIV-1核酸检测研究方法。本评论的目的是总结当前及其他用于PrEP实施的HIV检测方法，以指导各项目的最佳实践。
在PrEP使用者中诊断HIV-1具有挑战性，原因如下：（1）PrEP使用者中突破性HIV-1感染罕见，增加了检测假阳性的风险；（2）PrEP对急性HIV感染有影响；（3）在检测基础设施不完善的社区环境中提供PrEP。当前的最佳实践表明，应按照国家检测算法和世界卫生组织（WHO）的建议，使用快速诊断检测或自我检测。使用核酸检测，如血浆HIV-1 RNA聚合酶链反应，可能有助于更早地检测HIV-1，但可行性和假阳性风险是其缺点。检测血浆中单拷贝HIV-1 RNA和血液单核细胞中整合型前病毒DNA的敏感检测方法，可能是在研究环境中解决HIV-1诊断不明确问题的重要方法。延迟诊断可能会导致在长效PrEP选择下出现耐药性，而单次未经证实的假阳性检测可能会给长效PrEP使用者带来诊断挑战。HIV检测的成本、可行性和阳性预测值是PrEP项目的重要考虑因素。
检测不同PrEP方案使用者中HIV-1感染的最佳策略正在不断发展。虽然WHO的新指南建议在使用PrEP时通过血清学检测或自我检测来检测HIV-1，但仍需要针对PrEP突破性感染罕见病例和诊断不明确情况的可行临床管理计划。PrEP研究和扩大规模的数据将有助于我们评估不同检测方法和检测途径在纳入不同PrEP方案的HIV检测算法中的价值。
