Department of Pharmacy Practice, University at Buffalo, Buffalo, NY, USA.
Taichung Veterans General Hospital, Taichung, Taiwan.
Curr Top Behav Neurosci. 2021;50:517-545. doi: 10.1007/7854_2020_186.
The etiology and pathogenesis of human immunodeficiency virus type-I (HIV)-associated neurocognitive disorders (HAND) remain undetermined and are likely the produce of multiple mechanisms. This can mainly include neuronal injury from HIV, inflammatory processes, and mental health issues. As a result, a variety of treatment options have been tested including NeuroHIV-targeted regimens based on the central nervous system (CNS) penetration effectiveness (CPE) of antiretroviral therapy (ART) and adjuvant therapies for HAND. NeuroHIV-targeted ART regimens have produced consistent and statistically significant HIV suppression in the CNS, but this is not the case for cognitive and functional domains. Most adjuvant therapies such as minocycline, memantine, and selegiline have negligible benefit in the improvement of cognitive function of people living with HIV (PLWH) with mild to moderate neurocognitive impairment. Newer experimental treatments have been proposed to target cognitive and functional symptoms of HAND as well as potential underlying pathogenesis. This review aims to provide an analytical overview of the clinical treatment options and clinical trials for HAND by focusing on NeuroHIV-targeted ART regimen development, CPE, and adjuvant therapies.
人类免疫缺陷病毒 1 型（HIV）相关神经认知障碍（HAND）的病因和发病机制仍未确定，可能是多种机制共同作用的结果。这主要包括 HIV 对神经元的损伤、炎症过程和心理健康问题。因此，已经测试了多种治疗选择，包括基于抗逆转录病毒治疗（ART）的中枢神经系统（CNS）穿透效果（CPE）的针对 NeuroHIV 的治疗方案和 HAND 的辅助治疗。针对 NeuroHIV 的 ART 方案在 CNS 中产生了一致且具有统计学意义的 HIV 抑制，但在认知和功能领域并非如此。大多数辅助治疗方法，如米诺环素、美金刚和司来吉兰，对改善轻度至中度神经认知障碍的 HIV 感染者（PLWH）的认知功能几乎没有益处。已经提出了新的实验性治疗方法来针对 HAND 的认知和功能症状以及潜在的发病机制。本综述旨在通过关注针对 NeuroHIV 的 ART 方案的开发、CPE 和辅助治疗，对 HAND 的临床治疗选择和临床试验提供分析概述。
