This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although highly active anti-retroviral therapy (HAART) has markedly reduced the morbidity and mortality of HIV-infected children, the improved life expectancy is associated with a complex set of metabolic disorders in a subset of patients. These disorders include growth failure with lower lean body mass (LBM). Although the clinical features of this metabolic derangement is described, its mechanistic underpinnings are unknown. It is important to delineate these mechanisms in order to establish new therapies for pediatric patients because growth failure will lead to stunting. In this project we plan to test the hypothesis that HIV-infected children have a lower LBM due to a deficit in net protein synthesis because of upregulated protein catabolism. To test this hypothesis we propose to conduct stable isotope tracer experiments to achieve the following specific aim: measure lean body mass (LBM) and protein kinetics in HIV-infected prepubertal children versus age-and gender-matched HIV-exposed children and determine the effect of dietary energy and protein supplementation on LBM and protein kinetics in the HIV-infected group. Despite an adequate dietary protein intake, HIV-infected children have a lower LBM due to a deficit in the availability of endogenous protein to support LBM synthesis. This decreased protein availability is secondary to a chronic upregulation of protein catabolism relative to intake. We further propose that this condition can be ameliorated by dietary supplementation with more energy and protein. Measure body composition and protein kinetics in prepubertal HIV-infected children versus age and gender matched HIV-exposed children and determine the effect of dietary energy and protein supplementation on protein kinetics in the HIV-infected group.
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