Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy

Background: Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen in patients receiving antiretroviral combination therapy (ART). Howev er, the underlying mechanisms and long-term risks (e.g., cardiovascular eve nts) are still unclear. Objectives/Methods: In 5 patients with ART-associated dyslipidemia, stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days wa s used to investigate the metabolism of apolipoprotein B-containing lipopro teins (very low density lipoproteins [VLDL](1), VLDL2, intermediate density lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with those in 6 healthy normolipidemic controls. Results: The patients under ART showed significantly increased fasting trig lycerides (359 vs. 77 mg/dl) and VLDL (54 vs. 15 mg/dl), compared with cont rols. They had significantly higher total cholesterol (213 vs. 157 mg/dl) a nd then was a nonsignificant trend toward higher LDL (136 vs. 93 mg/dl), an d toward lower HDL (26 vs. 46 mg/dl). The ratio of large, buoyant LDL, over small, dense LDL, was markedly reduced in patients under ART (0.80 vs. 2.0 0). Total apo B synthesis was significantly increased (25.5 vs. 14.5 mg/kg/ d) and shifted, toward triglyceride rich VLDL1 (18.5 vs. 8.7 mg/kg/d) in pa tients receiving ART. There was also a significantly reduced rate of apo B lipoprotein transfer from VLDL1 to VLDL2 (3.7 vs. 20.7 pools/d). In additio n, all patients revealed insulin resistance. Conclusions: These data indicate that increased triglycerides in HIV-infect ed patients with ART are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase-mediated d elipidation. In addition, total apo B synthesis was increased and shifted t oward triglyceride-rich VLDL1. Overall, this lipoprotein profile in patient s with ART-associated dyslipidemia implies an increased risk for cardiovasc ular events.