DataSheet_2_Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk.pdf

IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).
MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors.
ResultsIn total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only.
ConclusionHIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

引言
阐明炎症模式是理解人类免疫缺陷病毒（HIV）感染及其相关心血管疾病（CVD）病理生理学的核心前提。本研究旨在解析HIV感染相关炎症模式，并通过颈动脉内膜中层厚度（CIMT）评估受试者的心血管疾病风险。

方法
本研究在南非约翰内斯堡开展横断面研究，纳入接受抗反转录病毒治疗（ART）且病毒学抑制的HIV阳性参与者，以及以HIV阳性参与者的家属或朋友为招募来源的HIV阴性对照者。研究收集了受试者的心血管疾病危险因素及CIMT相关数据。采用Olink炎症检测面板，可同时定量检测92种炎症标志物。通过主成分分析（PCA）与协方差分析（ANCOVA），探究HIV阳性与HIV阴性参与者的炎症模式差异。采用校正经典心血管疾病危险因素的线性回归模型，分析经ANCOVA筛选得到的差异免疫标志物对CIMT的影响。

结果
本研究共纳入185名HIV阳性参与者及104名HIV阴性参与者，总受试者289名，其中女性占比63%，中位年龄为40.7岁（四分位数间距IQR：35.4~47.7岁）。与HIV阴性参与者相比，HIV阳性参与者年龄更高（平均高出6岁，p<0.01），且CIMT水平显著升高（p<0.01）。主成分分析未识别出明确的炎症模式。经协方差分析筛选，共9种免疫标志物在HIV阳性与HIV阴性参与者间存在显著差异，其中包括PDL1。PDL1与CIMT存在独立相关性，但经分层分析后发现，该相关性仅存在于HIV阴性参与者中。

结论
接受稳定ART治疗的HIV阳性患者与HIV阴性对照者的免疫激活模式无显著差异。本研究纳入的炎症标志物可介导HIV阳性参与者的心血管疾病风险。