Department of Cancer Immunology and Virology.
Department of Data Science, Dana-Farber Cancer Institute.
AIDS. 2023 Nov 15;37(14):2137-2147. doi: 10.1097/QAD.0000000000003675. Epub 2023 Jul 27.
Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on antiretroviral therapy (ART). Vascular disease contributes to HAND, but peripheral markers that distinguish vascular cognitive impairment (VCI) from HIV-related etiologies remain unclear.
Cross-sectional study of vascular injury, inflammation, and central nervous system (CNS) injury markers in relation to HAND.
Vascular injury (VCAM-1, ICAM-1, CRP), inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF-A), and CNS injury (NFL, total Tau, GFAP, YKL-40) markers were measured in plasma and CSF from 248 individuals (143 HIV+ on suppressive ART and 105 HIV- controls).
Median age was 53 years, median CD4 + cell count, and duration of HIV infection were 505 cells/μl and 16 years, respectively. Vascular injury, inflammation, and CNS injury markers were increased in HIV+ compared with HIV- individuals ( P < 0.05). HAND was associated with increased plasma VCAM-1, ICAM-1, and YKL-40 ( P < 0.01) and vascular disease ( P = 0.004). In contrast, inflammation markers had no significant association with HAND. Vascular injury markers were associated with lower neurocognitive T scores in age-adjusted models ( P < 0.01). Furthermore, plasma VCAM-1 correlated with NFL ( r = 0.29, P = 0.003). Biomarker clustering separated HAND into three clusters: two clusters with high prevalence of vascular disease, elevated VCAM-1 and NFL, and distinctive inflammation profiles (CRP/ICAM-1/YKL-40 or IL-6/IL-8/IL-15/MCP-1), and one cluster with no distinctive biomarker elevations.
Vascular injury markers are more closely related to HAND and CNS injury in PWH on suppressive ART than inflammation markers and may help to distinguish relative contributions of VCI to HAND.
尽管抗逆转录病毒疗法（ART）可抑制病毒，但人类免疫缺陷病毒（HIV）相关的神经认知障碍（HAND）仍然普遍存在。血管疾病是 HAND 的一个致病因素，但外周标志物仍不清楚，无法区分血管性认知障碍（VCI）和 HIV 相关病因。
横断面研究与 HAND 相关的血管损伤、炎症和中枢神经系统（CNS）损伤标志物。
从 248 名个体（143 名 HIV+接受抑制性 ART，105 名 HIV-对照）的血浆和脑脊液中测量血管损伤（VCAM-1、ICAM-1、CRP）、炎症（IFN-γ、IL-1β、IL-6、IL-8、IL-15、IP-10、MCP-1、VEGF-A）和中枢神经系统损伤（NFL、总 Tau、GFAP、YKL-40）标志物。
中位年龄为 53 岁，中位 CD4+细胞计数和 HIV 感染持续时间分别为 505 个/μl 和 16 年。与 HIV-个体相比，HIV+个体的血管损伤、炎症和中枢神经系统损伤标志物均增加（P < 0.05）。HAND 与血浆 VCAM-1、ICAM-1 和 YKL-40 升高有关（P < 0.01）和血管疾病（P = 0.004）。相反，炎症标志物与 HAND 无显著相关性。在年龄调整模型中，血管损伤标志物与较低的神经认知 T 评分相关（P < 0.01）。此外，血浆 VCAM-1 与 NFL 相关（r = 0.29，P = 0.003）。生物标志物聚类将 HAND 分为三个簇：两个簇有较高的血管疾病患病率，升高的 VCAM-1 和 NFL，以及独特的炎症谱（CRP/ICAM-1/YKL-40 或 IL-6/IL-8/IL-15/MCP-1），一个簇没有明显的生物标志物升高。
在接受抑制性 ART 的 PWH 中，血管损伤标志物与 HAND 和中枢神经系统损伤的相关性比炎症标志物更密切，可能有助于区分 VCI 对 HAND 的相对贡献。
