1st International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 26–28 June 1999 - San Diego, CA, USA

INCREASED APO B SYNTHESIS AND DEFECTIVE DELIPIDATION OF TRIGLYCERIDE-RICH VLDL ARE POTENTIAL MECHANISMS OF ART-ASSOCIATED DYSLIPIDAEMIA

Antiviral Therapy 1999; 4(Suppl. 2):59(abstract no. 47)

M Schmitz, G Michl, R Walli, T Demant and FD Goebel
Ludwig-Maximilians-Universitiy, Munich, Germany

BACKGROUND: Dyslipidaemia (predominantly hypertriglyceridaemia) is frequently seen under ART. However, the underlying mechanisms, and the long-term risks (e.g. cardiovascular events) are still unclear.

OBJECTIVES/METHODS: In five patients with ART-associated dyslipidaemia and insulin resistance, stable isotype-labelled amino acid tracer (d₃-Leu) kinetic analysis over 12 days was used to investigate the metabolism of apolipoprotein B-containing lipoproteins (VLDL₁, VLDL₂, IDL and LDL). Data were compared to eight HIV-negative normolipidaemic controls.

RESULTS: The patients under ART showed significantly increased fasting triglycerides (359 versus 65 mg/dl) and VLDL (54 versus 14 mg/dl), as compared to the controls. There was a non-significant trend towards higher total cholesterol (213 versus 174 mg/dl) and LDL (136 versus 112mg/dl), and towards lower HDL (26 versus 47mg/dl). The ratio of large, buoyant LDL₁ over small, dense LDL₂ was markedly reduced in patients under ART (0.80 versus 2.26). Total Apo B synthesis was significantly increased (25.5 versus 15.8 mg/kg/day) and shifted towards triglyceride rich VLDL₁ (18.5 versus 8.8 mg/kg/day) in patients under ART. There also was a significantly reduced rate of Apo B lipoprotein transfer from VLDL₁ to VLDL₂ (3.7 versus 20.7 mg/day).

CONCLUSIONS: These data indicate that increased triglycerides are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase mediated delipidation. In addition, total Apo B synthesis was increased and shifted towards triglyceride rich VLDL₁. Overall, this lipoprotein profile in patients with ART-associated dyslipidaemia implies an increased risk for cardiovascular events.

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