OBJECTIVE:To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth. DESIGN:Cross-sectional design within a prospective, 15-site US-based cohort study. METHODS:Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores. RESULTS:Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs. CONCLUSION:Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.

译文

目的:探讨围产期感染HIV(PHIV)和未患围产期HIV但未感染(PHEU)的年轻人中血管功能障碍标志物与神经发育结果之间的关系。
设计:一项前瞻性,位于美国的15个研究对象的队列研究中的横断面设计。
方法:评估了342名青年(212名PHIV,130名PHEU)中9种选择的血管生物标志物的神经发育结局。评估血清中的脂联素,C反应蛋白(CRP),纤维蛋白原,白介素6(IL-6),可溶性血管细胞粘附分子1(sVCAM-1),E选择素(sE-selectin),单核细胞趋化因子蛋白(sMCP-1),细胞间粘附分子1(sICAM-1)和P-选择素(sP-选择素)。韦氏儿童智力量表(第四版)(WISC-IV)在入学时进行管理,产生了智商全面得分和四个指数得分。进行因子分析以将生物标志物减少到具有相关生物学作用的较少因子。使用结构方程模型(SEM)来衡量结果因素与WISC-IV得分之间的关​​联。
结果:平均参与者年龄为11.4岁,女性为54%,黑人为70%。九种生物标志物被分为三个因子组:F1(纤维蛋白原,CRP和IL-6); F1(纤维蛋白原,CRP和IL-6); F1(纤维蛋白原,CRP和IL-6)。 F2(sICAM-1和sVCAM-1);和F3(MCP-1,sP-选择素和sE-选择素)。脂联素与任何因素均无相关性。扫描电镜显示在整个队列中F1与WISC-IV处理速度得分显着负相关。调整HIV状况和其他潜在的混杂因素后,这种效果仍然很明显。在未经调整和调整后的扫描电子显微镜中,仅限于PHIV参与者时,观察到类似的关联。
结论:总的纤维蛋白原,CRP和IL-6的测定指标可能是潜在的生物标志物,与HIV和PHEU青年的加工速度相对降低有关。

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