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Pathophysiology of dyslipidemia and increased cardiovascular risk in HIV lipodystrophy: a model of ‘systemic steatosis’

Balasubramanyam, Ashoka; Sekhar, Rajagopal Va; Jahoor, Farookb; Jones, Peter Hc; Pownall, Henry Jc

Current Opinion in Lipidology: February 2004 - Volume 15 - Issue 1 - pp 59-67
Nutrition and metabolism

Purpose of review: This review addresses a syndrome of dyslipidemia and lipodystrophy that has emerged in HIV-infected patients receiving highly active antiretroviral therapy (HAART). The term ‘HIV/HAART associated dyslipidemic lipodystrophy (HADL)’ describes this syndrome. Although HAART increases patient survival rates, their increased longevity and dyslipidemias place them at risk for cardiovascular disease. Identification of rationally based therapies requires an understanding of the mechanistic basis of HADL.

Recent findings: A case definition for HIV lipodystrophy, based on age, gender, duration of HIV disease, serum HDL cholesterol and anthropometry, provides high diagnostic sensitivity and specificity. The dyslipidemias, mainly hypercholesterolemia, hypertriglyceridemia and low-plasma HDL cholesterol, among HIV-infected patients in the pre- and post-HAART eras are summarized. Clinical studies of HADL patients show increased lipolysis, which increases free fatty acid transfer to liver for incorporation into lipoprotein triglycerides that are secreted, and to skeletal muscle where they impair normal insulin signaling. A model of HADL that includes preferential lipolysis in femoral-gluteal fat depots is presented. Relevant therapies include those that inhibit lipolysis (niacin) or increase hepatic fatty acid oxidation (fibrates).

Summary: HADL is one of several disorders characterized by dyslipidemia, insulin resistance, and lipodystrophy. The relative acuteness of HADL should facilitate identification of the sequence of metabolic changes that gives rise to the syndrome. Current evidence suggests that deranged energy storage in femoral-gluteal and other peripheral sites is important; the molecular details for the derangement are unknown but are under scrutiny by many investigators.

aDivision of Endocrinology, bChildren's Nutritional Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA and cSection of Atherosclerosis and Lipoprotein research

Correspondence to Henry J. Pownall, MS A601, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Tel.: 713 798 4160; fax: 713 798 4121; e-mail; hpownall@bcm.tmc.edu.

Abbreviations FFA: free fatty acid HAART: highly active antiretroviral therapy HADL: HIV/HAART associated dyslipidemic lipodystrophy HDL-C: HDL cholesterol IRS-1: insulin receptor substrate-1 LPL: lipoprotein lipase NRTI: nucleoside reverse transcriptase inhibitor

© 2004 Lippincott Williams & Wilkins, Inc.