HIV-protease inhibitor therapy has been effective at reducing HIV viral burden in many infected patients. However, the protease inhibitors have been associated with several metabolic complications. The prevalence of hyperglycemia, hypertriglyceridemia, and hypercholesterolemia has increased as more HIV-infected patients are treated with protease inhibitors. We propose to characterized the hyperglycemia or hypertriglyceridemia or hypercholesterolemia that occurs in HIV-protease ingibitor treated subjects by comparing their fasting concentrations of selected hormones that regulate glucose and lipid metabolism to the following groups of subjects: (a) not infected with HIV, (b) HIV-infected but not treated with HIV-protease inhibitors, (c) HIV-infected and treated with HIV-protease inhibitors but who do not develop hyperglycemia, hypertriglyceridemia, or hypercholesterolemia, and (d) HIV-infected who develop diabetes or lipid disorders while receiving a protease inhibitor, but then are switched to an antiretroviral regimen that includes a different or no HIV-protease inhibitors. We will further characterized the endocrine regulators of glycemic control in these subjects during an oral glucose challenge. We will examine whether the hypertiglyceridemia and hypercholesterolemia that develops in subjects treated with and HIV-protease inhibitor is associated with increased heparin-releasable lipoprotein lipase activity (LPL). This experimental paradigm fits in well with the ACTU and ID Clinic Treatment strategies. This should allow us to recruit enough subjects who develop these metabolic disorders as well as the appropriate control subjects who are treated with protease ingibitors, but don't develop the metabolic disorders. It will also allow us to study the same parameters in the same subjects while treated with a protease inhibitors, and then switched to a different antiviral regimen that presumably will not be associated with the metabolic disorder. This may help identify which protease ingibitors or antiretroviral therapies are most associated with diabetes and lipid disorders in HIV-infected subjects.
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