Fibrinogen is positively associated with mortality in HIV-infected MAPK inhibitor individuals [31], but whether this translates to increased CVD risk is unclear. PI therapy was associated with increased fibrinogen levels in the Fat Redistribution and Metabolic Change Study (FRAM) [39]. We found that fibrinogen was positively correlated with LDL-cholesterol levels in HIV-infected children. Fibrinogen may represent coagulation risk, but may also reflect inflammation. Several studies in adults have reported

associations between endothelial dysfunction markers and HIV disease severity [40, 41]. We found that MCP-1, sICAM, and sVCAM levels were higher in the HIV-infected children compared with the HEU children, and that higher levels were associated with viral load, independent of metabolic status. These findings suggest that HIV itself may cause immune activation and resulting endothelial injury [41]. These biomarkers are associated with all-cause mortality in

non-HIV-infected populations [42] and sVCAM levels are associated with increased carotid intima media thickness (cIMT) in HIV-infected adults [43]. The HIV trans-activator of transcription (Tat) selleck inhibitor and negative regulatory factor (Nef) proteins induce VCAM-1, ICAM-1 and MCP-1. ICAM was elevated in HIV-infected ADP ribosylation factor children compared with controls and elevations were inversely related to CD4 cell counts [44]. In addition, MCP-1 is thought to activate viral infection [45]. Treatment interruptions are associated with increased levels of sVCAM, ICAM and P-selectin [46], suggesting the influence of viral activity on expression of these biomarkers. We did not find a strong effect of ARVs on the biomarkers

we studied, possibly as a consequence of the collinearity of the effect of ARVs on metabolic outcomes. PI therapy was associated with higher fibrinogen and NNRTI was associated with higher CRP. In cell culture, ARVs can alter endothelial cell mitochondrial DNA, thereby increasing the production of reactive oxygen species [47, 48], endothelial cell permeability [49], and leucocyte adhesion [50]. Thus, ARV therapy could directly or indirectly (through changes in the metabolic profile) increase levels of biomarkers. Studies on vascular inflammation and structural/functional vascular dysfunction (i.e. vessel compliance, distensibility and structure) in HIV-infected children have been limited [51-56]. We have recently shown that similar biomarkers are also associated with central adiposity and decreased immune function (lower CD4 cell counts), although we had limited ability to evaluate the effect of lipids on these biomarkers [22].