The etiology and optimal treatment options of the HIV-associated metabolic syndrome, characterized by body fat redistribution, hyperlipidemia, and insulin resistance have not yet been fully elucidated. However, the mere presence of these metabolic abnormalities suggests increased risk for developing atherosclerotic cardiovascular disease, particularly given the prolonged survival due to HAART regimens. This research proposal includes two complementary studies (an observational study and a clinical trial) focusing on the HIV metabolic syndrome. The overall objective of the observational study is to identify whether serum resistin levels are an independent predictor for the development of insulin resistance, hyperlipidemia, and fat redistribution in HIV-infected subjects treated with antiretroviral agents and whether resistin interacts with other hormonal predictors such as leptin and adiponectin. This study consists of two parts: a cross-sectional sub-study aiming at determining associations of resistin levels with metabolic abnormalities, and a longitudinal sub-study assessing the role of baseline resistin levels in predicting development and progression of constituents of the HIV metabolic syndrome after a one-year interval. The interventional study is a 2x2 factorial, randomized, double blind, placebo-controlled clinical trial designed to identify whether fenofibrate arid/or pioglitazone administration improves hyperlipidemia, insulin resistance, glycemic control, lipodystrophic changes, and atherosclerosis associated with antiretroviral use in HIV-infected patients.
