Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
HIV Med. 2021 Apr;22(4):273-282. doi: 10.1111/hiv.13012. Epub 2020 Nov 5.
Premature development of cardiovascular disease in children living with HIV-1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH.
This was a cross-sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC ) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein-1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin-6 (IL-6)] and endothelial activation [angiopoietin-2 (Ang2), soluble vascular endothelial growth factor-1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme-linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways.
Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL-6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein-1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir-boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7-17, P = 0.0020).
Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r.
HIV-1 感染者（CLWH）的心血管疾病在儿童期过早发生，可能与肠道屏障功能受损、微生物易位、免疫激活、全身炎症和内皮激活有关。这些途径的生物标志物可能为 CLWH 动脉粥样硬化疾病的发病机制提供深入了解。
这是一项对参加多中心早期儿科启动-加拿大儿童治愈队列（EPIC）的 CLWH 的横断面研究，这些患者正在接受抗逆转录病毒治疗（ART），病毒载量无法检测到。通过酶联免疫吸附试验定量检测血浆生物标志物，包括肠上皮损伤[肠脂肪酸结合蛋白-1（IFABP）]、全身炎症[肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）]和内皮激活[血管生成素-2（Ang2）、可溶性血管内皮生长因子-1（sVEGFR1）和可溶性内皮糖蛋白（sEng）]。使用相关和因子分析来检验固有免疫途径之间的关联。
在 90 名 CLWH 中，有 16%的 Ang2、15%的 sVEGFR1 和 23%的 sEng 水平相对健康的历史对照升高。内皮激活的三个标志物之间的两两秩相关具有统计学意义（ρ=0.69、ρ=0.61 和 ρ=0.65，所有相关均 P<0.001）。通过对三个内皮生物标志物进行因子分析得出的内皮激活指数与 TNF（ρ=0.47，P<0.001）、IL-6（ρ=0.60，P<0.001）和肠脂肪酸结合蛋白-1（ρ=0.67，P<0.001）相关。目前或过去使用利托那韦增强洛匹那韦（LPV/r）治疗与内皮激活相关（比值比=5.0，95%CI：1.7-17，P=0.0020）。
尽管联合 ART 抑制了病毒，但 CLWH 仍存在内皮激活，且与肠上皮损伤、全身炎症和 LPV/r 治疗有关。
