Relative Effects of Insulin Resistance and Protease Inhibitor Treatment on Lipid and Lipoprotein Metabolism in HIV-Infected Patients

Abstract

Background: The relationship between insulin resistance, dyslipidemia, HIV infection, and antiretroviral therapy remains unclear, and the atherogenic nature of lipid and lipoprotein profiles in HIV-infected patients has not been fully characterized. Method: We measured plasma lipid and lipoprotein subfractions using Vertical Auto Profile-II methodology and directly measured insulin-mediated glucose disposal in 45 protease inhibitor (PI)-treated and non-PI-treated HIV-infected patients. Results: PI-treated patients had higher total, LDL, and narrow-density LDL cholesterol (p < .05) and a trend toward higher triglycerides, whereas HDL cholesterol and LDL particle characteristics were unrelated to PI use or history of lipodystrophy. Insulin sensitivity did not differ on the basis of PI therapy, but decreased insulin sensitivity was associated with lower HDL and HDL-3 cholesterol (p < .01); elevated triglyceride (p < .01), VLDL 1+2, and VLDL 3a+3b lipoproteins (p < .01); and smaller, denser (more atherogenic) LDL particle characteristics (p < .01). Thus, the lipoprotein abnormality associated with PI use was increased LDL cholesterol, whereas changes in TG and HDL metabolism were associated with insulin resistance, independent of PI use. Conclusion: The variables of PI-treatment, dyslipidemia, lipodsytrophy, and insulin resistance do not always cluster together in HIV-infected patients, which suggests that the metabolic phenotype emerging in treated patients results from a complex interplay of drug effects, immune restoration, and baseline insulin sensitivity.