With greater use of highly active antiretroviral therapy (HAART) in HIV-infected children, adverse metabolic abnormalities have increased both in prevalence and scope. Evidence suggests that adults with HIV infection are at an increased risk of developing premature atherosclerotic CV disease associated with abnormal metabolic profiles. However, far less is known about CV risk in children with HIV. Ongoing chronic inflammation that results from chronic immune activation in HIV-infected individuals may impair vascular endothelial function and further increase the risk of CV disease. Data regarding metabolic syndrome and vascular endothelial dysfunction in HIV-infected children is limited. Therefore, we are proposing a study to understand the extent of vascular dysfunction and identify potential HIV-specific risk factors. We also propose an intervention to treat adverse CV risk factors (endothelial dysfunction, adverse metabolic profiles) and improve clinical outcomes such as quality of life).
In Specific Aim 1, we will prospectively recruit 100 HIV- infected children and 100 of their siblings into a cross-sectional study evaluating vascular inflammatory pathways (biomarkers of inflammation, endothelial dysfunction, pro-coagulants and metabolic dysfunction) and vascular dysfunction (through flow-mediated vasodilation studies [FMD] and carotid intimal medial thickness) and will correlate levels with body composition (fat redistribution), lipids and insulin resistance (HOMA-IR scores).
In Specific Aim 2, we will determine the effect of a 12-week (2 visits per week) combined resistance and aerobic exercise intervention on nutritional, CV, and clinical outcomes for HIV-infected children. HIV- infected children (from Aim 1) will be equally divided into an active exercise intervention (40) and attention control (40) groups [goal is 25 per group]. This group will be offered the intervention after 3 months. Baseline studies of maximal myocardial oxygen uptake, vascular endothelial dysfunction (studies reviewed above), body composition, lipids, insulin resistance, quality of life and compliance will be compared at baseline, 3 months (at the end of the intervention), and 6 months (3 months after the intervention is completed). Through this study we will determine the extent of vascular dysfunction and its associations with metabolic parameters and will determine whether a structured exercise program positively changes these abnormalities in HIV-infected children.
Through this study we will determine the extent of vascular dysfunction and its associations with metabolic parameters and will determine whether a structured exercise program positively changes these abnormalities in HIV-infected children.
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