HIV Protease Inhibitor-Induced Lipodystrophy Syndrome

Human immunodeficiency virus (HIV) protease inhibitor (PI) therapy can cause a syndrome of lipodystrophy (peripheral fat wasting and/or central fat accumulation), hyperlipidaemia and insulin resistance. Type 2 diabetes mellitus appears to be a related, but less common, toxicity. Lipodystrophy occurs with all licensed, potent PIs after a median of about 10 months PI therapy. Any relationship to non-PI therapy or HIV disease appears limited. The syndrome may be due to the inhibition of two lipid regulatory proteins that have substantial homology to the catalytic site of HIV protease, namely cytoplasmic retinoic acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). There are no validated, objective diagnostic criteria at present but measurement of body fat mass may be useful. There is no proven therapy for any component of the syndrome. The full clinical significance of the syndrome is unknown but, in addition to the cosmetic effect, metabolic disturbances may increase the risk of longterm cardiovascular disease.