Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children

Miller, T. I.; Borkowsky, W.; DiMeglio, L. A.; Dooley, L.; Geffner, M. E.; Hazra, R.; McFarland, E. J.; Mendez, A. J.; Patel, K.; Siberry, G. K.; Van Dyke, R. B.; Worrell, C. J.; Jacobson, D. L.; Shearer, W.; Cooper, N.; Harris, L.; Purswani, M.; Baig, M.; Cintron, A.; Puga, A.; Navarro, S.; Patton, D.; Burchett, S.; Karthas, N.; Kammerer, B.; Yogev, R.; Malee, K.; Hunter, S.; Cagwin, E.; Wiznia, A.; Burey, M.; Nozyce, M.; Chen, J.; Gobs, E.; Grant, M.; Knapp, K.; Allison, K.; Garvie, P.; Acevedo-Flores, M.; Rios, H.; Olivera, V.; Silio, M.; Borne, C.; Sirois, P.; Spector, S.; Norris, K.; Nichols, S.; McFarland, E.; Barr, E.; Chambers, C.; Watson, D.; Messenger, N.; Belanger, R.; Dieudonne, A.; Bettica, L.; Adubato, S.; Scott, G.; Himic, L.; Willen, E.

HIV Med. 2011 Dec 6; 13(5):264-75


OBJECTIVES: 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.

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