HIV protease inhibitors and obesity

Abstract

Purpose of review: To review the current scientific literature and recent clinical trials on HIV protease inhibitors and their potential role in the pathogenesis of lipodystrophy and metabolic disorders.

Recent findings: HIV protease inhibitor treatment may affect the normal stimulatory effect of insulin on glucose and fat storage. Further, chronic inflammation from HIV infection and protease inhibitor treatment trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. This process leads to a pathologic cycle of lipodystrophy and lipotoxicity, a proatherogenic lipid profile, and a clinical phenotype of increased central body fat distribution similar to the metabolic syndrome.

Summary: Protease inhibitors are a key component of antiretroviral therapy and have dramatically improved the life expectancy of HIV-infected individuals. However, they are also associated with abnormalities in glucose/lipid metabolism and body fat distribution. Further studies are needed to better define the pathogenesis of protease inhibitor-associated metabolic and body fat changes and their potential treatment.

Figure 1. A schema for the development of HIV/PI-associated lipodystrophy and its associated adverse effects

Abbreviations: 11β-HSD1, 11β-hydroxysteroid dehydrogenase type 1; FFA, free fatty acids; HIV, human immunodeficiency virus; PI, protease inhibitor; ROS, reactive oxygen species; TG, triglyceride.