Some HIV-infected adults develop a lipodystrophy that includes significant changes in body shape, with fat loss in the face, arms and legs, and fat gain in the trunk. This lipodystrophy is often accompanied by hypertriglyceridemia, hypercholesterolemia, and hyperinsulinemia. So far, almost all cases of lipodystrophy have occurred in patients treated with protease inhibitor-containing antiretroviral therapies. Whether this lipodystrophy is a result of the use of protease inhibitors or other therapies employed for HIV infection, or is one of the many manifestations of HIV infection, and is unmasked by the longevity achieved by those treated with protease inhibitors remains uncertain. It has been suggested, although not proven, that this condition may be an adverse effect of protease inhibitor treatment. It is also unknown whether HIV-infected children develop significant lipodystrophy when exposed to protease inhibitors. We propose to investigate whether initiation of protease inhibitor-containing antiretroviral regimens in children with HIV infection affects the prevalence of dyslipidemia, insulin resistance, and alterations of body fat distribution, and to study the pathophysiology of these changes. The incidence of such abnormalities will be compared to children with non-HIV-related chronic infections, to HIV-infected children who are treated with protease inhibitor sparing regimen, and to healthy controls.~This study has both cross-sectional and longitudinal components. Children with HIV infection, who are to begin taking protease inhibitors and who are already taking protease inhibitors as part of their treatment for HIV infection, will be recruited for a single cross-sectional evaluation that will include studies of lipid and glucose metabolism and body composition. In the longitudinal component, those children with HIV infection, who were studied before they began taking protease inhibitors, will be followed prospectively for 18 months to delineate further the relationships between treatment and the development of lipodystrophy and abnormalities in lipid and glucose metabolism. If the cross-sectional study does not show that the prevalence of lipodystrophy and its associated metabolic alterations increases as a function of exposure to protease inhibitors, we will terminate the prospective study. Changes in triglyceride levels, insulin levels, and regional body fat will be evaluated as primary outcome measures. As part of the evaluations performed during the cross-sectional and longitudinal studies, we will investigate the pathophysiology of dyslipidemia in HIV-infected children by assessing lipoproteins and their subclasses, apolipoproteins, and both lipoprotein lipase levels and activity.
Some HIV-infected adults develop lipodystrophy that includes significant changes in body shape, with fat losses in the face, arms and legs, and fat gain in the trunk. This lipodystrophy is often accompanied by other disorders of metabolism, such as increased levels of fat and insulin in the blood.~The majority of these cases have been seen when patients are taking medications called protease inhibitors. These are anti-retroviral medications designed to treat patients with HIV. It is unclear if lipodystrophy is a result of having HIV or the medication used to treat HIV. It has been suggested, but not proven, that lipodystrophy is a direct side effect of protease inhibitors. In addition, it is unknown if HIV-infected children develop significant lipodystrophy after taking protease inhibitors.~This study will investigate the prevalence of metabolic disorders and changes in body fat distribution in children taking protease inhibitor anti-retroviral medications. The results will be compared to three other groups; (1) children suffering from other non-HIV chronic infections, (2) HIV-infected children not taking protease inhibitors, and (3) healthy children.~The study will look at HIV-infected children who have already started taking protease inhibitors. It will evaluate these children for disorders in metabolism as well as body fat changes. In addition, the study will follow HIV-infected children who will begin taking protease inhibitors. The study will follow these children for 18 months to detect the development of disorders in metabolism and / or body fat changes.