PATHOPHYSIOLOGY OF HIV AND ITS MANAGEMENT

Pathophysiology of HIV and its management

Pathophysiology of HIV and its management

Introduction

A characteristic dyslipidemic pattern observed in the majority of patients with HLS is moderate to severe hypertriglyceridemia and reduced serum HDL cholesterol, with serum LDL cholesterol that is slightly elevated or altered in composition to small, dense particles. This resembles the typical dyslipidemia of the Metabolic Syndrome, albeit in an accelerated and exaggerated form. Indeed, insulin resistance and increased cardiovascular risk have been associated with HLS in several studies. A subset of these patients also manifest generalized lipoatrophy or truncal fat accumulation associated with peripheral lipoatrophy. (Gao, 1999, 436)

Pathophysiology of HIV and its management: A Case Analysis

We have previously proposed, on the basis of whole body lipid kinetic data, a pathophysiologic scheme whereby fundamental defects in adipocyte function lead to a chain of metabolic consequences that explain hypertriglyceridemia, insulin resistance and increased cardiovascular risk in HLS. The mechanisms associated with depotspecific adipose alterations, i.e., atrophy in some regions and hypertrophy in others, are not easy to explain on the basis of whole-body metabolic measurements and they require investigations of lipid turnover in specific body regions, which are currently under way. Metabolic basis of HLS - studies in the fasting and fed state: Whole body kinetic studies have demonstrated defects in specific lipid metabolic pathways in HLS patients in both the fasting and fed states. Studies in the fasted state uniformly reveal accelerated whole body lipolysis in patients with different phenotypic forms of HLS. Sekhar et al. studied patients with the “mixed” form (i.e., with peripheral atrophy and central obesity) of HLS using infusions of 13C1-palmitate, 2H2-glycerol and indirect calorimetry and showed that, compared to age-, gender- (Gao, 1999, 436) and BMI-matched non-HIV healthy controls, these patients had markedly increased rates of both total and net lipolysis. Despite a modest concomitant increase in the rate of intra-adipocyte reesterification, there was a net excess release of free fatty acids (FFA's) into the plasma pool. The HLS patients lacked the ability to increase fat oxidation proportionately, resulting in a net increase in hepatic flux of FFA's resulting in increased availability of FFAs for hepatic reesterification and increased release of VLDLtriglyceride into the circulation. Reeds et al. confirmed the latter finding by direct measurement of the rate of VLDL-triglyceride synthesis in HLS patients. Another fate of un-oxidized plasma FFA's derived from excessive lipolysis would be increased deposition of fatty acids in myocytes and hepatocytes. (Bailes, 2003, 1713)

Indeed, excessive intramyocellular fat has been noted in patients with HLS and this is strongly associated with the development of insulin resistance in skeletal muscle. An indirect correlate of this effect is that the FFA's that form the substrate for fat oxidation in HLS patients are derived mainly from non-plasma sources such as intramyocellular lipid depots. Finally, elevated plasma FFA's in HLS patients would also exacerbate an atherogenic plasma lipid profile by increasing the activity of cholesteryl ester transfer protein, which catalyzes transfer of triglycerides of VLDL to HDL and ...