Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, L69 7BE, UK.
Wirral University Teaching Hospital NHS Foundation Trust, Arrowe Park Wirral, Birkenhead, CH49 5PE, UK.
J Neurovirol. 2021 Feb;27(1):80-85. doi: 10.1007/s13365-020-00917-1. Epub 2021 Jan 6.
The aim of this study is to ascertain the burden of pre-clinical atherosclerotic changes in the brains of young adult males with HIV and explore the impact of anti-retroviral therapy (ART). The study design is case-control, cross-sectional. Histological sections from HIV-positive post-mortem brain samples, with no associated opportunistic infection, from the MRC Edinburgh brain bank were evaluated. These were age and sex matched with HIV-negative controls. Immunohistochemical stains were performed to evaluate characteristics of atherosclerosis. The pathological changes were graded blinded to the HIV status and a second histopathologist reassessed 15%. Univariable models were used for statistical analyses; p ≤ 0.05 was considered significant. Nineteen HIV-positive post-mortem cases fulfilled our inclusion criteria. Nineteen HIV-negative controls were selected. We assessed mostly small-medium-sized vessels. For inflammation (CD45), 7 (36%) of the HIV+ had moderate/severe changes compared with none for the HIV- group (p < 0.001). Moderate/severe increase in smooth muscle remodeling (SMA) was found in 8 (42%) HIV+ and 0 HIV- brains (p < 0.001). Moderate/severe lipoprotein deposition (LOX-1) was found in 3 (15%) and 0 HIV-brains (p < 0.001). ART was associated with less inflammation [5 (63%) no ART versus 2 (18%) on ART (p = 0.028)] but was not associated with reduced lipid deposition or smooth muscle damage. In HIV infection, there are pre-clinical small- to medium-sized vessel atherosclerotic changes and ART may have limited impact on these changes. This could have implications on the increasing burden of cerebrovascular disease in HIV populations and warrants further investigation.
本研究旨在确定 HIV 阳性年轻成年男性大脑中临床前动脉粥样硬化变化的负担,并探讨抗逆转录病毒治疗 (ART) 的影响。该研究设计为病例对照、横断面研究。评估了来自 MRC 爱丁堡大脑银行的 HIV 阳性尸检脑样本的组织学切片,这些样本没有相关的机会性感染,与 HIV 阴性对照组相匹配。进行了免疫组织化学染色以评估动脉粥样硬化的特征。病理变化在不知道 HIV 状态的情况下进行盲法评估,由第二位组织病理学家对 15%的样本进行重新评估。使用单变量模型进行统计分析;p≤0.05 被认为具有统计学意义。19 例符合纳入标准的 HIV 阳性尸检病例。选择了 19 例 HIV 阴性对照。我们主要评估了中小血管。对于炎症(CD45),7 例(36%)HIV+病例的变化为中度/重度,而 HIV-组无一例为中度/重度(p<0.001)。8 例(42%)HIV+和 0 例 HIV-大脑中发现平滑肌重塑(SMA)中度/重度增加(p<0.001)。3 例(15%)和 0 例 HIV-大脑中发现中等/重度脂蛋白沉积(LOX-1)(p<0.001)。ART 与炎症减少相关[5 例(63%)无 ART 与 2 例(18%)ART(p=0.028)],但与脂质沉积或平滑肌损伤无关。在 HIV 感染中,存在临床前小至中等大小血管的动脉粥样硬化变化,ART 可能对这些变化的影响有限。这可能对 HIV 人群中不断增加的脑血管疾病负担产生影响,需要进一步研究。