AIDS-related lipodystrophy/insulin resistance syndrome.
The recent development and clinical use of three different types of highly effective anti-HIV-1 drugs, including nucleotide and non-nucleotide reverse transcriptase inhibitors (NRTIs) and non-peptidic viral protease inhibitors (PIs) and their combinations, termed highly active antiretroviral therapy (HAART), have dramatically reduced the infection-related mortality of AIDS patients in developed countries. However, the prolongation of the life expectancy of HIV-1-infected patients and/or long-term use of the above antiviral agents have generated a score of new problems and complications. Among them is the relatively common AIDS-related lipodystrophy/insulin resistance syndrome, which is associated with severe metabolic disturbances such as carbohydrate intolerance/diabetes mellitus and severe dyslipidemia, which influence the quality of life and threaten the life expectancies of HIV-1-infected patients by increasing the risk of atherosclerotic cardiovascular disease. The etiology of this syndrome appears to be multi-factorial; the classes of anti-viral drugs listed above, hypercytokinemia in AIDS patients, and the HIV-1 infection itself could induce the pathologic changes of this syndrome or increase the vulnerability of patients to the adverse effect of the therapeutic compounds. In this article, we review our current understanding of the pathogenesis of this severe AIDS-associated metabolic disorder.
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. kinot@mail.nih.gov
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D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D016207:Cytokines / Q000502:physiology; D015696:Gene Products, tat / Q000502:physiology; D016336:Gene Products, vpr / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology; D017320:HIV Protease Inhibitors / Q000009:adverse effects; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology / Q000628:therapy; D006801:Humans; D024821:Metabolic Syndrome / Q000209:etiology / Q000628:therapy; D028361:Mitochondrial Diseases / Q000150:complications; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D015696:Gene Products, tat; D016336:Gene Products, vpr; D005938:Glucocorticoids; D017320:HIV Protease Inhibitors; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1