HIV-infected patients increasingly demonstrate metabolic abnormalities, including dyslipidemia, insulin resistance and body composition abnormalities that may predispose to cardiovascular disease (CVD). Novel preliminary data from our laboratory suggest that inflammation is significant among patients with HIV lipodystrophy, and may contribute independently to CAD risk in this population. The optimal strategy as to how to treat the metabolic abnormalities in the HIV population has not yet been determined. In prior studies in this grant, we have demonstrated the efficacy of combined strategies including metformin and resistance training to markedly improve metabolic endpoints including waist to hip ratio (WHR) and parameters of insulin resistance to a greater degree than metformin alone. In addition, we now show in preliminary data a significant effect of lifestyle modification on glucose, blood pressure and waist circumference over 6 months with excellent adherence to a rigorous lifestyle prescription, designed in conjunction with the Diabetes Prevention Program Investigators. In the revised renewal application, we will test the hypothesis that novel and traditional cardiovascular risk factors, including inflammation, contribute to cardiovascular disease and endothelial dysfunction, even among young HIV-infected patients. Detailed assessment of cross-sectional and longitudinal markers of coronary and carotid plaque will be made, assessing the independent effects of inflammation and traditional risk factors. As a second Aim in the revised competitive renewal application, we will compare lifestyle modification alone, metformin alone, both and neither, in a four-arm study among HIV-infected patients with the metabolic syndrome, as suggested by the Reviewers. We hypothesize that these strategies will not only improve individual risk factors, but also improve IMT, plaque progression and endothelial function. We will furthermore investigate the effects of lifestyle modification to alter inflammatory indices through effects on body composition and whether improvement in inflammatory indices relates to the improvement in endovascular disease. Lay description: The proposed grant will assess if HIV-infected patients have increased risk factors for heart disease. In addition, the grant will test whether changes in diet, exercise and metformin improves these risks and reduces atherosclerotic disease in the blood vessels. ? ? ?
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