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Am J Physiol Endocrinol Metab 280: E549-E553, 2001;
0193-1849/01 $5.00
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Vol. 280, Issue 4, E549-E553, April 2001

INVITED REVIEW
Adverse metabolic consequences of HIV protease inhibitor therapy: the search for a central mechanism

Paul W. Hruz1,2, Haruhiko Murata1, and Mike Mueckler1

Department of 1 Cell Biology and Physiology and 2 Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110

Although the clinical introduction of human immunodeficiency virus (HIV) protease inhibitors (PIs) has resulted in a dramatic decline in HIV-related morbidity and mortality, it is now recognized that PI therapy is associated with serious adverse metabolic effects, including peripheral lipoatrophy, increased visceral fat, hyperlipidemia, and insulin resistance. Despite increasing awareness of this metabolic syndrome, the etiology of these side effects remains obscure. This review critically examines current mechanistic hypotheses in the context of the available experimental data. To date, a single unifying explanation for this syndrome has not been confirmed. As data accumulate, it is becoming clear that PIs lack precision in their cellular targets and it is likely that many of the side effects of these drugs are due to inhibition of a number of unrelated molecules.

human immunodeficiency virus; lipodystrophy; metabolic complications; adipogenesis; glucose transport


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