Mezoh Genevieve, Lutchman Nereshni, Worsley Catherine, Gededzha Maemu, Mayne Elizabeth, Martinson Neil, Moore Penny L, Crowther Nigel J
Department of Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Chemical Pathology, National Health Laboratory Service, Johannesburg, South Africa.
AIDS Res Hum Retroviruses. 2022 Feb;38(2):152-161. doi: 10.1089/AID.2021.0052. Epub 2022 Jan 25.
The prevalence of cardiovascular death in the HIV-infected population is higher than in uninfected individuals. Growing evidence suggests that HIV infection itself is directly linked to endothelial activation and dysfunction. Therefore, the aim of this study was to investigate whether endothelial activation is present in African subjects with HIV infection and identify its possible determinants. Eighty HIV-infected treatment-naive cases, categorized into two groups based on CD4 count (38 subjects with CD4 count ≤350 cells/mm and 42 subjects with CD4 count >350 cells/mm), were compared with 60 HIV-uninfected controls. A small subgroup of the HIV-infected participants ( = 13) were followed up for 18 months following initiation of antiretroviral therapy (ART). Anthropometric data, fasting lipid and glucose levels, viral load, and CD4 counts were measured as were serum levels of intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1, von Willebrand factor (vWF), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). The HIV-infected low CD4 group had higher levels of ICAM-1 ( < .05), VCAM-1 ( < .0005), TNF-α ( < .005), and vWF ( < .005), compared with the controls. In the HIV-infected cohort, VCAM-1 levels were negatively associated with CD4 counts (β = -0.474; < .0005), whereas vWF levels were positively associated with viral load (β = 0.344; < .01). Levels of ICAM-1 and VCAM-1 were reduced by ART ( < .05 vs. baseline for both), however, levels of IL-6, IL-8, and TNF-α increased ( < .005 vs. baseline for all). Endothelial activation and inflammation are evident in African ART-naive HIV-infected patients; the former is attenuated, and the latter is increased after 18 months of ART. In HIV-infected subjects, both immunological dysregulation and viral load are associated with biomarkers of endothelial activation.
HIV感染人群中心血管疾病死亡的患病率高于未感染个体。越来越多的证据表明，HIV感染本身与内皮细胞激活和功能障碍直接相关。因此，本研究的目的是调查非洲HIV感染受试者中是否存在内皮细胞激活，并确定其可能的决定因素。将80例未经治疗的HIV感染病例根据CD4细胞计数分为两组（38例CD4细胞计数≤350个细胞/mm³，42例CD4细胞计数>350个细胞/mm³），与60例未感染HIV的对照者进行比较。一小部分HIV感染参与者（n = 13）在开始抗逆转录病毒治疗（ART）后随访18个月。测量了人体测量数据、空腹血脂和血糖水平、病毒载量、CD4细胞计数以及细胞间黏附分子-1（ICAM-1）、内皮白细胞黏附分子-1、血管细胞黏附分子-1（VCAM-1）、单核细胞趋化蛋白-1、血管性血友病因子（vWF）、肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）的血清水平。与对照组相比，HIV感染低CD4组的ICAM-1（P <.05）、VCAM-1（P <.0005）、TNF-α（P <.005）和vWF（P <.005）水平更高。在HIV感染队列中，VCAM-1水平与CD4细胞计数呈负相关（β = -0.474；P <.0005），而vWF水平与病毒载量呈正相关（β = 0.344；P <.01）。ART使ICAM-1和VCAM-1水平降低（两者均与基线相比P <.05），然而，IL-6、IL-8和TNF-α水平升高（均与基线相比P <.005）。在未经ART治疗的非洲HIV感染患者中，内皮细胞激活和炎症明显；前者在ART治疗18个月后减弱，后者增强。在HIV感染受试者中，免疫失调和病毒载量均与内皮细胞激活的生物标志物相关。
