Despite the availability of modern antiretroviral therapy (ART), neurocognitive impairment persists among some persons with HIV (PWH). We investigated the role of exposure to four major classes of ARTs in neurocognitive impairment in PWH. A single-site cohort of 343 PWH was recruited. Lifetime ART medication history was obtained from medical health records. We evaluated the role of ART exposure as a predictor of neurocognitive impairment using univariate analyses and machine learning, while accounting for potential effects of demographic, clinical, and comorbidity-related risk factors. Out of a total of 26 tested variables, two random forest analyses identified the most important characteristics of a neurocognitively impaired group (N = 59): Compared with a neurocognitively high-performing group (N = 132; F₁-score = 0.79), we uncovered 13 important risk factors; compared with an intermediate-performing group (N = 152; F₁-score = 0.75), 16 risk factors emerged. Longer lifetime ART exposure, especially to integrase inhibitors, was one of the most important predictors of neurocognitive impairment in both analyses (rank 2 of 13 and rank 4 of 16, respectively), superseding effects of age (rank 11/13, rank 15/16) and HIV duration (rank 13/13, rank 16/16). Concerning specific integrase inhibitors, the impaired group had significantly longer dolutegravir exposure (p = 0.011) compared with the high-performing group (p = 0.012; trend compared with the intermediate group p = 0.063). A longer duration to integrase inhibitor intake was negatively related to cognition in this cohort. Our findings suggest that possible cognitive complications of long-term exposure to integrase inhibitors, in particular dolutegravir, should be closely monitored in PWH.

尽管可以使用现代抗逆转录病毒疗法 (ART)，但某些 HIV 感染者 (PWH) 仍存在神经认知障碍。我们调查了暴露于四类主要 ART 在 PWH 神经认知障碍中的作用。招募了 343 名 PWH 的单站点队列。终身 ART 用药史是从医疗健康记录中获得的。我们使用单变量分析和机器学习评估了 ART 暴露作为神经认知障碍预测因子的作用，同时考虑了人口统计学、临床和合并症相关风险因素的潜在影响。在总共 26 个测试变量中，两个随机森林分析确定了神经认知受损组 ( N  = 59)的最重要特征： 与神经认知高表现组相比 (N  = 132；F ₁ -score = 0.79)，我们发现了 13 个重要的风险因素；与中等表现组（N  = 152；F ₁ -score = 0.75）相比，出现了 16 个风险因素。更长寿命的 ART 暴露，尤其是整合酶抑制剂，是两项分析中神经认知障碍最重要的预测因素之一（分别为 13 名中的第 2 名和 16 名中的第 4 名），取代年龄的影响（第 11/13 名，第 15 名/ 16) 和 HIV 持续时间（排名 13/13，排名 16/16）。关于特定的整合酶抑制剂， 与高性能组相比，受损组 ( p = 0.011) 的多替拉韦暴露时间显着延长( p  = 0.012；与中间组相比的趋势)p  = 0.063）。在该队列中，整合酶抑制剂摄入时间较长与认知呈负相关。我们的研究结果表明，在 PWH 中应密切监测长期接触整合酶抑制剂（尤其是多替拉韦）可能出现的认知并发症。