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Investigation into the mechanism and treatment of atherogenic dyslipidemia in HIV + patients with HIV metabolic syndrome

University of British Columbia

The use of highly active combination anti-retroviral therapy is associated with serious metabolic side effects including increased serum triglycerides, decreased HDL cholesterol as well as insulin resistance, peripheral fat loss and gain of abdominal visceral fat. There is concern that anti-retroviral therapy imposes a significant risk of heart disease in the HIV positive population. We hypothesize that development of dyslipidemia in response to anti-retroviral therapy is associated with the presence of specific genetic polymorphisms and may relate to changes in lipoprotein lipase and hepatic lipase levels. We have assessed a number of biochemical and genetic markers in a cohort of HIV+ subjects with dyslipidemia. In our cohort lipoprotein lipase is significantly decreased (36.03 ± 30.17 nmol/min/ml vs. 86.79 ± 63.96 nmol/min/ml, p<0.01) and hepatic lipase is significantly increased (225.15 ± 104.60 nmol/min/ml vs. 139.02 ± 40.89 nmol/min/ml, (p < 0.05) compared to healthy controls. As well, our cohort had significantly elevated serum lipids (total cholesterol 7.2 mmol/L, HDL-C 0.9 mmol/L, TG 7.8 mmol/L, TC/HDL-C 8.5). 12% of the subjects in our cohort had fasting glucose levels above 7 mmol/L, the cut-off for a diagnosis of diabetes. There was no association between the polymorphisms of LPL (Asn291Ser), ApoE (4/4, 4/3, 3/3, 3/2, 2/2), or Apo CIII (SstI G3238C) and serum lipids in our cohort. In our cohort fibrates significantly decreased serum triglycerides (37%, p=0.028) while fibrates, in combination with statins significantly decreased serum triglycerides and total cholesterol (52%, p=0.002 and 20%, p=0.007 respectively). There were no significant changes in serum HDL, or in the ratio of total to HDL cholesterol in either of the treatment groups. Supplementation with fish oil did not improve serum lipids compared to placebo. In conclusion, while we have not demonstrated an association between selected polymorphisms of LPL, apo E or apo C-III, we have demonstrated that LPL activity is decreased and HL activity is increased in our cohort of HIV+ patients with dyslipidemia. We believe that the combination of risk factors identified in our study, and results of previous studies, suggest that this cohort is at significantly increased risk of coronary artery disease.

Thesis/Dissertation

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2009-11-18

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http://hdl.handle.net/2429/15246

Pathology

University of British Columbia

UBCV

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