Anti-lipolytic Therapy for HIV Lipodystrophy

Massachusetts General Hospital, Boston MA

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Abstract

DESCRIPTION (provided by applicant): HIV-infected patients treated with highly active antiretroviral therapy (HAART) are at increased risk for developing significant dyslipidemia, insulin resistance and abnormal patterns of fat distribution. While the exact mechanism responsible for these changes is not known, there is increasing evidence that patients with HIV infection and fat redistribution have increased basal rates of lipolysis and elevated circulating free fatty acids (FFA). Patients with HIV-associated lipodystrophy have increased FFA levels that correlated directly with impaired glucose metabolism and triglyceride concentrations. Furthermore, acute inhibition of lipolysis in patients with HIV lipodystrophy and insulin resistance results in improvement in insulin sensitivity. However, long-term administration of lipolytic blocking agents has not been evaluated in this patient population. Acipimox, a nicotinic acid analogue and a potent inhibitor of lipolysis, is an established therapy for dyslipidemia. In addition, through effects on lowering circulating FFA, acute administration of acipimox has been shown to improve insulin sensitivity in other populations including lean and obese individuals and patients with type II diabetes. We hypothesize that chronic administration of acipimox will improve hyperlipidemia and insulin sensitivity among HIV infected patients experiencing HAART-associated metabolic disturbances. We propose a 3-month randomized, double-blind, placebo-controlled trial of acipimox in HIV infected patients with fat redistribution in order to determine the effects of acipimox on lipolysis, glucose homeostasis and body composition. The proposed study will provide valuable preliminary data assessing the utility of an anti-lipolytic strategy to treat the metabolic complications of HAART as well as potential insight into the mechanism of these disturbances. Together, these data will be used to develop future long-term studies to evaluate the efficacy and safety of anti-lipolytic strategies in HIV infected patients with HAART-associated metabolic abnormalities and fat redistribution.