Centre for Immunity, Infection and Immunity, Ashworth Laboratories, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh, EH9 3JT, Scotland, UK.
J Neurovirol. 2014 Feb;20(1):28-38. doi: 10.1007/s13365-013-0225-3. Epub 2014 Jan 14.
The long-term impact of chronic human immunodeficiency virus (HIV) infection on brain status in injecting drug users (IDU) treated with highly active antiretroviral therapy (HAART) is unknown. Viral persistence in the brain with ongoing neuroinflammation may predispose to Alzheimer-like neurodegeneration. In this study, we investigated the brains of ten HAART-treated individuals (six IDU and four non-DU), compared with ten HIV negative controls (six IDU and four non-DU). HIV DNA levels in brain tissue were correlated with plasma and lymphoid tissue viral loads, cognitive status, microglial activation and Tau protein and amyloid deposition. Brain HIV proviral DNA levels were low in most cases but higher in HIV encephalitis (n = 2) and correlated significantly with levels in lymphoid tissue (p = 0.0075), but not with those in plasma. HIV positive subjects expressed more Tau protein and amyloid than HIV negative controls (highest in a 58 year old), as did IDU, but brain viral loads showed no relation to Tau and amyloid. Microglial activation linked significantly to HIV positivity (p = 0.001) and opiate abuse accentuated these microglial changes (p = 0.05). This study confirms that HIV DNA persists in brains despite HAART and that opiate abuse adds to the risk of brain damage in HIV positive subjects. Novel findings in this study show that (1) plasma levels are not a good surrogate indicator of brain status, (2) viral burden in brain and lymphoid tissues is related, and (3) while Tau and amyloid deposition is increased in HIV positive IDU, this is not specifically related to increased HIV burden within the brain.
慢性人类免疫缺陷病毒（HIV）感染对接受高效抗逆转录病毒治疗（HAART）的注射吸毒者（IDU）的大脑状况的长期影响尚不清楚。病毒在大脑中的持续存在伴随着持续的神经炎症，可能导致类似阿尔茨海默病的神经退行性变。在这项研究中，我们研究了 10 名接受 HAART 治疗的个体（6 名 IDU 和 4 名非 IDU）的大脑，与 10 名 HIV 阴性对照（6 名 IDU 和 4 名非 IDU）进行了比较。脑组织中的 HIV 前病毒 DNA 水平与血浆和淋巴组织病毒载量、认知状态、小胶质细胞激活以及 Tau 蛋白和淀粉样蛋白沉积相关。大多数情况下，脑内 HIV 前病毒 DNA 水平较低，但在 HIV 脑炎（n=2）中较高，并且与淋巴组织中的水平显著相关（p=0.0075），但与血浆中的水平无关。HIV 阳性受试者表达的 Tau 蛋白和淀粉样蛋白高于 HIV 阴性对照组（最高的是一名 58 岁的受试者），IDU 也是如此，但脑内病毒载量与 Tau 和淀粉样蛋白无相关性。小胶质细胞激活与 HIV 阳性显著相关（p=0.001），阿片类药物滥用加重了这些小胶质细胞的变化（p=0.05）。这项研究证实，尽管接受了 HAART，HIV DNA 仍在大脑中持续存在，阿片类药物滥用增加了 HIV 阳性受试者大脑损伤的风险。本研究的新发现表明：（1）血浆水平不是大脑状况的良好替代指标，（2）脑和淋巴组织中的病毒负担相关，（3）虽然 HIV 阳性 IDU 中 Tau 和淀粉样蛋白沉积增加，但这与脑内 HIV 负担的增加并无特异性相关。
