Department of Laboratory Medicine, San Francisco VA Health Care System, San Francisco, CA, USA.
University of California, San Francisco, San Francisco, CA, USA.
Curr Top Behav Neurosci. 2021;50:77-103. doi: 10.1007/7854_2019_100.
Neurocognitive impairment caused by chronic human immunodeficiency virus (HIV) infection is a growing concern. In this chapter we discuss the inflammatory mechanisms underlying the pathology of asymptomatic and mild neurocognitive impairment in the context of antiretroviral therapy. We discuss the role of HIV, viral proteins, and virally infected cells on the development of neuroinflammation and the effect of viral proteins on the cells of the central nervous system.We examine how these collective factors result in an inflammatory context that triggers the development of neurocognitive impairment in HIV. We assess the contribution of antiretrovirals and drugs of abuse, including methamphetamine, cannabis, and opioids, to the neurotoxic and neuroinflammatory milieu that leads to the development of neurocognitive impairment in HIV-infected individuals. We also examined circulating biomarkers, NF-L, sCD163, and sCD14, pertinent to identifying changes in the CNS that could indicate real-time changes in patient physiology. Lastly, we discuss future studies, such as exosomes and the microbiome, which could play a role in the HIV-induced neuroinflammation that eventually manifests as cognitive impairment.
慢性人类免疫缺陷病毒（HIV）感染引起的神经认知障碍是一个日益受到关注的问题。在本章中，我们将讨论在抗逆转录病毒治疗的背景下，无症状和轻度神经认知障碍病理的炎症机制。我们讨论了 HIV、病毒蛋白和被病毒感染的细胞在神经炎症发展中的作用，以及病毒蛋白对中枢神经系统细胞的影响。我们研究了这些综合因素如何导致炎症环境，从而引发 HIV 患者的神经认知障碍。我们评估了抗逆转录病毒药物和药物滥用（包括甲基苯丙胺、大麻和阿片类药物）对导致 HIV 感染者发生神经认知障碍的神经毒性和神经炎症环境的贡献。我们还检查了与识别 CNS 变化相关的循环生物标志物，如 NF-L、sCD163 和 sCD14，这些标志物可以指示患者生理的实时变化。最后，我们讨论了可能在 HIV 诱导的神经炎症中发挥作用的未来研究，如外泌体和微生物组，这些炎症最终表现为认知障碍。
