HIV lipodystrophy syndrome is associated with both metabolic (dyslipidemia, insulin resistance) and anthropomorphic (lipoatrophy, central obesity) abnormalities. These defects are likely to predispose HIV patients on highly active antiretroviral therapy (HAART) to accelerated cardiovascular morbidity. On the basis of our data on key mechanisms of altered lipid kinetics in these patients, evidence that diet and exercise patterns of patients with HIV-lipodystrophy are inadequate to manage cardiovascular risk factors, and current recommendations for treatment of atherosclerosis and insulin resistance, we hypothesize that: 1) an intensive lifestyle intervention with diet and exercise will improve the plasma lipid profile, decrease visceral fat mass and improve hormonal, metabolic and lipoprotein markers associated with insulin resistance; and 2) adding niacin, fenofibrate, or a combination of the two drugs to the intensive lifestyle intervention will result in further improvement in the cardiovascular risk profile. We propose a randomized, placebo-controlled clinical trial in 200 hypertriglyceridemic HIV patients on stable HAART treatment with the following Specific Aims: 1) To compare the effects of usual care; intensive diet and exercise (DE); DE + niacin; DE + fenofibrate; and DE + niacin + fenofibrate on fasting plasma lipid concentrations (Primary endpoint); 2) To compare the effects of the five treatment protocols on body fat distribution; 3) To compare the effects of the five treatment protocols on hormonal, lipoprotein and metabolic markers of insulin resistance. Our collaborative team has expertise in lipid and lipoprotein metabolism, innovative and effective diet modification programs, intensive exercise programs in HIV patients, and clinical trials of antilipidemic and antiretroviral agents. Thus, this study will determine the efficacy of diet and exercise, with and without niacin and fenofibrate, in reducing the cardiovascular risk of patients with HIV lipodystrophy / dyslipidemia.

R01HL073696

2003-09-01

2010-07-31