title: Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children.
abstract: OBJECTIVE
  HIV-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction in HIV-infected children (with and without hyperlipidaemia) with those in HIV-exposed, uninfected (HEU) children enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers.
  
  
  METHODS
  A prospective cohort study was carried out. Biomarkers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP1)], coagulant dysfunction (fibrinogen and P-selectin), endothelial dysfunction [soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM) and E-selectin], and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded.
  
  
  RESULTS
  The median ages of the children were 12.3 years in the HIV-infected group and 10.1 years in the HEU group. Body mass index (BMI) z-scores, waist and hip circumferences, and percentage body fat were lower in the HIV-infected children. Total and non-high-density lipoprotein (HDL) cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children also had higher MCP-1, fibrinogen, sICAM and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavourable lipid profiles were positively associated with IL-6, MCP-1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP-1 and CRP) and endothelial dysfunction (sICAM and sVCAM).
  
  
  CONCLUSIONS
  HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavourable lipid levels and active HIV replication.
authors.affiliation: Department of Pediatrics, Division of Pediatric Clinical Research, Miller School of Medicine at the University of Miami, Miami, FL, USA.
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mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D002648:Child; D015331:Cohort Studies; D019040:E-Selectin / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D015658:HIV Infections / Q000097:blood* / Q000503:physiopathology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D019007:P-Selectin / Q000097:blood; D012307:Risk Factors; D014779:Virus Replication / Q000502:physiology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D019040:E-Selectin; D015850:Interleukin-6; D019007:P-Selectin; D005340:Fibrinogen; D002097:C-Reactive Protein