HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment.
HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment.
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DOI：
10.1038/nrneurol.2016.27
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
McArthur JC
中科院分区：
文献类型：
--
作者：
Saylor D;Dickens AM;Sacktor N;Haughey N;Slusher B;Pletnikov M;Mankowski JL;Brown A;Volsky DJ;McArthur JC
在过去二十年中，一些进步改善了对艾滋病毒感染者的护理。最重要的是，联合抗逆转录病毒疗法（CART）的发展和部署导致艾滋病死亡率大幅下降，因此，如果接受CART治疗，今天的艾滋病毒感染者的预期寿命几乎正常。术语HIV相关神经认知障碍（HAND）已被用于描述与HIV感染相关的神经认知功能障碍谱。HIV可在感染的早期进入CNS，持续的CNS HIV感染和炎症可能有助于HAND的发展。随后，大脑可以作为持续的HIV复制的避难所，即使在系统性病毒抑制已经实现的情况下。手可以留在接受CART治疗的患者体内，其对生存率、生活质量和日常功能的影响使其成为一个重要的未解决问题。在这篇综述中，我们描述了手的流行病学，其神经发病机制的不断发展的概念，从动物模型的新见解，和新的治疗方法。我们还讨论了慢性HIV感染中炎症是如何持续的。此外，我们认为，需要针对CNS炎症和其他代谢过程（包括谷氨酸稳态，脂质和能量代谢）的治疗来逆转或改善HAND相关的神经功能障碍。
In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies — treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism — are needed to reverse or improve HAND-related neurological dysfunction.