Neuropathogenesis of HIV-associated neurocognitive disorders: roles for immune activation, HIV blipping and viral tropism.
Neuropathogenesis of HIV-associated neurocognitive disorders: roles for immune activation, HIV blipping and viral tropism.
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DOI：
10.1097/coh.0000000000000105
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发表时间：
2014-11
影响因子：
4.1
通讯作者：
Kolson DL
中科院分区：
文献类型：
--
作者：
Chen MF;Gill AJ;Kolson DL
讨论为什么尽管高效抗逆转录病毒治疗（ART）明显有效地抑制了HIV，但HIV相关的神经认知障碍（HAND）仍然存在。多达50%的HIV感染者患有HAND，尽管在大多数接受治疗的个体中，ART将HIV复制抑制到明显检测不到的水平。在抗逆转录病毒疗法之前，艾滋病毒相关性痴呆（HAD）是HAND的最严重形式，影响了约20%的感染者; HAD现在只影响了约2%的抗逆转录病毒疗法治疗者，而不太严重的HAND形式仍然存在。最近的研究将ART治疗个体的持续免疫激活、炎症和病毒逃逸/水泡以及合并症与HIV疾病进展和HAND风险增加联系起来。尽管在大多数ART治疗的个体中持续的HIV抑制，通过常规血浆监测和偶尔的CSF监测表明，但HIV复制的“斑点”通常通过更频繁的监测被检测到，因此挑战了病毒抑制的概念。虽然HIV疱疹的原因尚不清楚，但CSF HIV疱疹与神经炎症和可能的CNS损伤有关。目前的理论，即嗜巨噬细胞的HIV病毒株在中枢神经系统中占主导地位，在驱动手和这些相关因素，现在也受到挑战。ART对CNS的保护是不完全的，可能是由于不完全的HIV抑制、持续的免疫激活和宿主共病因素的综合作用。辅助治疗ART是必要的更有效的保护。
To discuss why HIV-associated neurocognitive disorders (HAND) persist despite apparently effective HIV suppression by highly active antiretroviral therapy (ART). As many as 50% of HIV-infected individuals suffer from HAND despite ART suppression of HIV replication to apparently undetectable levels in most treated individuals. Prior to ART, HIV-associated dementia (HAD), the severest form of HAND, affected ~20% of infected individuals; HAD now affects only ~2% of ART-treated persons, while less severe HAND forms persist. Recent studies link persistent immune activation, inflammation, and viral escape/blipping in ART-treated individuals, as well as co-morbid conditions, to HIV disease progression and increased HAND risk. Despite sustained HIV suppression in most ART-treated individuals, indicated by routine plasma monitoring and occasional CSF monitoring, ‘blips’ of HIV replication are often detected with more frequent monitoring, thus challenging the concept of viral suppression. Although the causes of HIV blipping are unclear, CSF HIV blipping associates with neuroinflammation and, possibly, CNS injury. The current theory that macrophage-tropic HIV strains within the CNS predominate in driving HAND and these associated factors is now also challenged. Protection of the CNS by ART is incomplete, probably due to combined effects of incomplete HIV suppression, persistent immune activation, and host co-morbidity factors. Adjunctive therapies to ART are necessary for more effective protection.