Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus.
Use of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection is associated with the development of cardiovascular risk factors, including dyslipidemia, insulin resistance, fat redistribution, and hypertension. The results of the Data Collection on Adverse Events of Anti-HIV Drugs study showed that HAART therapy is associated with a 26% relative risk increase in the rate of myocardial infarction per year of HAART exposure. A number of studies have shown that insulin resistance often precedes lipodystrophy, suggesting that insulin resistance may be a primary feature of the metabolic syndrome in this population. The rate-limiting step in the uptake of glucose is glucose transport, and the predominant glucose transporter (GLUT) in muscle and fat is GLUT-4. Specific protease inhibitors (PIs) have been associated with decreased GLUT-4-mediated glucose transport and insulin resistance both in vitro and in vivo, whereas newer protease inhibitors may have fewer effects on insulin sensitivity. Data also suggest that endothelial dysfunction, impaired fibrinolysis, and excess inflammation may contribute to increased cardiovascular risk in the population infected with HIV. Moreover, recent data suggest that evidence for coronary atherosclerotic disease can be revealed by means of carotid intimal medial thickness (IMT) assessments in specific groups of HIV patients. Pharmacologic strategies for the prevention and/or treatment of HAART-induced dyslipidemia and abnormal glucose homeostasis include 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), resins, nicotinic acid, fibrates, and insulin-sensitizing agents. However, newer PIs such as atazanavir may result in less insulin resistance and dyslipidemia and, as part of a HAART regimen, use of atazanavir may reduce the metabolic complications associated with HAART.
Grinspoon
Steven K
SK
MGH Program in Nutritional Metabolism, Massachusetts General Hospital, 55 Fruit Street, LON 207, Boston, Massachusetts 02114-2696, USA. sgrinspoon@partners.org
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000139:chemically induced; D024821:Metabolic Syndrome / Q000139:chemically induced*; D009004:Monosaccharide Transport Proteins / Q000494:pharmacology; D009124:Muscle Proteins / Q000494:pharmacology; D012307:Risk Factors
D019380:Anti-HIV Agents; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D005947:Glucose