Background: HIV+ patients are at increased risk of cardiovascular disease (CVD). Chronic inflammation and endothelial dysfunction play a key role in adults, but have not been assessed in HIV+ children. We compared inflammation and endothelial markers in HIV+ children vs healthy controls, and assessed their relationship to carotid IMT (cIMT), an established marker for subclinical atherosclerosis.

Methods: We prospectively enrolled 27 HIV+ children and 30 age-matched HIV- healthy controls (2-20 yrs). Evaluations included measurements of internal carotid artery (ICA) and common carotid artery (CCA) IMT, as well as fasting lipids, insulin, inflammatory markers (TNF-a, soluble TNF receptors (sTNFRI, II), IL-6, high sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO)), and endothelial activation markers (soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF)). Wilcoxon rank sum was used to assess differences between groups. Spearman correlation coefficients were used to assess correlations. 

Results: In HIV+ group, median age was 10 yrs, 33% were males, 70% black. Groups were similar in age, race, sex, and BMI. 100% acquired HIV by vertical transmission with a mean CD4 count (CD4%) of 1058 (35%) cells/µL; 96% were on ART; 70% had HIV-1 RNA<50 copies/mL. Total cholesterol, LDL, HDL, insulin, and waist-to-hip ratio were higher in the HIV+ vs control group (all P<0.05). Inflammation and endothelial activation markers were similar between groups except for hsCRP, which was significantly higher in HIV+ (mean(SD) 6.12(10) vs 2.56(4.8) mg/L; P<0.001). Mean(SD) cIMT was similar between groups (CCA: HIV+ 0.87(0.01) vs HIV- 0.9(0.17) mm (P=0.4); ICA: HIV+ 0.74(0.15) vs HIV- 0.7(0.18) mm (P=0.3)). In HIV+, CCA IMT was correlated with vWF (R=0.42, P=0.03), sVCAM-1 (R=0.48, P=0.02), TNFRII (R=0.42, P=0.04), and IL-6 (R=0.5, P<0.01), and ICA was correlated with hsCRP (R=0.67, P<0.01). The endothelial marker, sVCAM-1 correlated with inflammatory markers, TNF-α, TNFRII, IL-6, and MPO. For controls, ICA was correlated with sVCAM-1 (R=0.40, P=0.03) but not with any inflammation markers. 

Conclusions: This study shows increased hsCRP in HIV+ children compared to matched controls. As we previously demonstrated in adults, inflammation markers were associated with cIMT and endothelial markers, which support a role for inflammation in endothelial activation and CVD in HIV-infected children.