Clinical review 159: Human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome: clinical presentation, pathophysiology, and therapeutic strategies.

Abstract

Obesity has been linked to insulin resistance (IR) and type 2 diabetes mellitus (DM) through epidemiological and clinical studies (1, 2). Interestingly, syndromes characterized by lipoatrophy and lipodystrophy are also associated with profound IR and metabolic abnormalities (3–5). Congenital and acquired forms of lipoatrophy and lipodystrophy, although rare, have been well described (6–8). Most recently, a lipodystrophic syndrome has been reported with increasing frequency in populations of HIV-infected individuals treated with highly active antiretroviral therapy (HAART; Ref. 5). This syndrome, similar to the congenital syndromes discussed briefly below, is also associated with significant metabolic abnormalities, including IR, type 2 DM, and hyperlipidemia. The fact that congenital lipodystrophy/atrophy syndromes and acquired syndromes such as HIV-associated lipodystrophy are both characterized by adipose tissue depletion or redistribution emphasizes the importance of the adipocyte in the pathogenesis of the associated metabolic disturbances. In this review, we provide a brief overview of our current understanding of the pathogenesis of IR and the associated metabolic abnormalities. Specifically, we provide our current state of knowledge of the HIV-associated lipodystrophy syndrome, including its clinical presentation, pathophysiology, and current and future therapeutic approaches.