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大脑中的人类免疫缺陷病毒——罪魁祸首还是帮凶?

Human Immunodeficiency Virus in the Brain-Culprit or Facilitator?

作者信息

Ene Luminita

机构信息

HIV Department, "Dr. Victor Babes" Hospital for Infectious and Tropical Diseases, Bucharest, Romania.

出版信息

Infect Dis (Auckl). 2018 Feb 14;11:1178633717752687. doi: 10.1177/1178633717752687. eCollection 2018.

Abstract

INTRODUCTION

Human immunodeficiency virus (HIV) enters the brain early, where it can persist, evolve, and become compartmentalized. Central nervous system (CNS) disease can be attributed to HIV alone or to the complex interplay between the virus and other neurotropic pathogens.

AIM

The current review aims to describe the direct impact of HIV on the brain as well as its relationship with other pathogens from a practitioner's perspective, to provide a general clinical overview, brief workup, and, whenever possible, treatment guidance.

METHODS

A review of PubMed was conducted to identify studies on neuropathogenesis of HIV in relation to host responses. Furthermore, the interaction between the CNS pathogens and the host damage responses were revised in the setting of advanced and also well-controlled HIV infection.

RESULTS

Similar to other pathogens, HIV leads to CNS immune activation, inflammation, and viral persistence. Therefore, almost half of the infected individuals present with neurocognitive disorders, albeit mild. Compartmentalized HIV in the CNS can be responsible in a minority of cases for the dramatic presentation of symptomatic HIV escape. Disruption of the immune system secondary to HIV may reactivate latent infections or allow new pathogens to enter the CNS. Opportunistic infections with an inflammatory component are associated with elevated HIV loads in the cerebrospinal fluid and also with greater cognitive impairment. The inflammatory immune reconstitution syndrome associated with CNS opportunistic infections can be a life-threatening condition, which needs to be recognized and managed by efficiently controlling the pathogen burden and timely balanced combination antiretroviral therapy. Latent neurotropic pathogens can reactivate in the brain and mimic HIV-associated severe neurological diseases or contribute to neurocognitive impairment in the setting of stable HIV infection.

CONCLUSIONS

As HIV can be responsible for considerable brain damage directly or by facilitating other pathogens, more effort is needed to recognize and manage HIV-associated CNS disorders and to eventually target HIV eradication from the brain.

摘要

引言

人类免疫缺陷病毒(HIV)早期即进入大脑,可在其中持续存在、演变并形成分隔状态。中枢神经系统(CNS)疾病可单独归因于HIV,也可归因于病毒与其他嗜神经病原体之间的复杂相互作用。

目的

本综述旨在从临床医生的角度描述HIV对大脑的直接影响及其与其他病原体的关系,提供总体临床概述、简要检查方法,并尽可能提供治疗指导。

方法

对PubMed进行检索,以确定关于HIV神经发病机制与宿主反应相关的研究。此外,还对晚期及病情得到良好控制的HIV感染情况下中枢神经系统病原体与宿主损伤反应之间的相互作用进行了综述。

结果

与其他病原体类似,HIV可导致中枢神经系统免疫激活、炎症和病毒持续存在。因此,近一半的感染者会出现神经认知障碍,尽管症状较轻。中枢神经系统中呈分隔状态的HIV在少数情况下可导致有症状的HIV逃逸的显著表现。HIV继发的免疫系统破坏可能会激活潜伏感染或使新的病原体进入中枢神经系统。伴有炎症成分的机会性感染与脑脊液中HIV载量升高以及更严重的认知障碍有关。与中枢神经系统机会性感染相关的炎症性免疫重建综合征可能是一种危及生命的情况,需要通过有效控制病原体负荷和及时进行平衡的联合抗逆转录病毒治疗来识别和处理。潜伏的嗜神经病原体可在大脑中重新激活,模仿与HIV相关的严重神经疾病,或在HIV感染稳定的情况下导致神经认知障碍。

结论

由于HIV可直接或通过促进其他病原体导致相当程度的脑损伤,因此需要付出更多努力来识别和处理与HIV相关的中枢神经系统疾病,并最终致力于从大脑中清除HIV。

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