Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Room 1001, Toronto, ON, M5S 3M2, Canada.
Fluids Barriers CNS. 2020 Jul 10;17(1):42. doi: 10.1186/s12987-020-00204-5.
HIV associated neurocognitive disorders (HAND) are the spectrum of cognitive impairments present in patients infected with human immunodeficiency virus type 1 (HIV-1). The number of patients affected with HAND ranges from 30 to 50% of HIV infected individuals and although the development of combinational antiretroviral therapy (cART) has improved longevity, HAND continues to pose a significant clinical problem as the current standard of care does not alleviate or prevent HAND symptoms. At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that it stems from neuronal injury due to chronic release of neurotoxins, chemokines, viral proteins, and proinflammatory cytokines secreted by HIV-1 activated microglia, macrophages and astrocytes in the central nervous system (CNS). Furthermore, the blood-brain barrier (BBB) not only serves as a route for HIV-1 entry into the brain but also prevents cART therapy from reaching HIV-1 brain reservoirs, and therefore could play an important role in HAND. The goal of this review is to discuss the current data on the epidemiology, pathology and research models of HAND as well as address the potential pharmacological treatment approaches that are being investigated.
HIV 相关神经认知障碍（HAND）是指人类免疫缺陷病毒 1 型（HIV-1）感染患者存在的认知障碍谱。受 HAND 影响的患者人数占 HIV 感染者的 30%至 50%，尽管联合抗逆转录病毒疗法（cART）的发展提高了患者的寿命，但 HAND 仍然是一个严重的临床问题，因为目前的护理标准无法缓解或预防 HAND 症状。目前，导致 HAND 的病理机制尚不清楚，但有证据表明，它源于由于慢性释放神经营养毒素、趋化因子、病毒蛋白和 HIV-1 激活的小胶质细胞、巨噬细胞和星形胶质细胞分泌的促炎细胞因子而导致的神经元损伤，在中枢神经系统（CNS）中。此外，血脑屏障（BBB）不仅是 HIV-1 进入大脑的途径，而且还阻止了 cART 治疗到达 HIV-1 大脑储库，因此它在 HAND 中可能发挥重要作用。本综述的目的是讨论 HAND 的流行病学、病理学和研究模型的现有数据，并探讨正在研究的潜在药物治疗方法。
