60 Pathogenesis of Dyslipidemia in HIV Lars Berglund Univ of California, Davis, USA

The introduction of Highly Active AntiRetroviral Therapy (HAART) represents a major breakthrough in HIV treatment, and increased use of this treatment strategy has resulted in considerably improved survival. However, the improved clinical picture in HIV-infected patients undergoing HAART is associated with significant metabolic side effects, such as body fat redistribution, dyslipidemia and insulin resistance. The dyslipidemic pattern seen during HAART has similar features to the metabolic syndrome, with presence of hypertriglyceridemia, low HDL cholesterol and an increase in LDL cholesterol levels. In addition, changes in HDL and LDL subpopulation pattern have been reported with a relative increase in the smaller particle distribution ranges for both lipoprotein fractions. Notably, small LDL is implicated as being more atherogenic than larger LDL, and the smaller HDL subpopulation are suggested to be less anti-atherogenic than larger HDL.

Our present understanding of the underlying mechanisms for the metabolic complications in HIV is not complete, although a number of studies have contributed to increase our knowledge in this area. It is likely that multiple pathways are involved and that the background for the metabolic pattern is complex. Further, there are drug-specific effects on lipoprotein levels. The similarity with features of the metabolic syndrome suggests that similar mechanisms may be involved. In insulin resistance, there is increasing focus on changes in muscle and hepatic lipid, glucose and energy metabolism resulting in hepatic steatosis and intramyocellular lipid accumulation. Changes in metabolite transport pathways, such as the Glut4 transporter have been found. Insulin resistance is also associated with an increase in free fatty acid levels and with an increase in visceral adiposity. However, presence of HIV, prior to introduction of HAART, has also been associated with lipoprotein abnormalities, such as low HDL cholesterol levels and hypertriglyceridemia, which at least partly have been ascribed to effects of an acute phase reaction. As the metabolic syndrome is a pro-inflammatory condition, studies to date suggest that an interaction of HIV, HAART, insulin resistance, inflammation, changes in lipid partitioning and mitochondrial function may contribute to the metabolic complications observed in HIV/HAART.