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Originally published In Press as doi:10.1194/jlr.M300041-JLR200 on June 16, 2003

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Journal of Lipid Research, Vol. 44, 1692-1697, September 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Increased VLDL-apoB and IDL-apoB production rates in nonlipodystrophic HIV-infected patients on a protease inhibitor-containing regimen

: a stable isotope kinetic study

Jean Michel Petit1,*,{dagger}, Michel Duong§, Emmanuel Florentin*, Laurence Duvillard*, Pascal Chavanet§, Jean Marcel Brun{dagger}, Henri Portier§, Philippe Gambert* and Bruno Vergès*,{dagger}

* Laboratoire de Biochimie and Institut National de la Santé et de la Recherche Médicale U498, Hôpital Universitaire du Bocage, 21000 Dijon, France
{dagger} Services d'Endocrinologie, Hôpital Universitaire du Bocage, 21000 Dijon, France
§ des Maladies Infectieuses, Hôpital Universitaire du Bocage, 21000 Dijon, France

1 To whom correspondence should be addressed. e-mail: jean-michel.petit{at}chu-dijon.fr

The aim of this study was to identify the first abnormalities of apolipoprotein B (apoB) metabolism in HIV-infected patients treated by antiretroviral therapy (ART) with protease inhibitors (PIs). The influence of ART on the metabolism of apoB in VLDL, IDL, and LDL was investigated in six patients receiving dual nucleoside reverse transcriptase inhibitors (NRTIs) and PI, and in five patients receiving NRTI and nevirapine. None of the patients had lipodystrophy. The study was performed in the fed state. Each subject received an intravenous injection of a 0.7 mg·kg-1 bolus of L-[1-13C]leucine, immediately followed by a 16 h constant infusion at 0.7 mg·kg-1·h-1. The VLDL- and IDL-apoB concentrations were significantly higher in PI-treated patients compared to non-PI-treated patients. The VLDL-apoB and IDL-apoB production rates were markedly higher in PI-treated patients compared to non-PI-treated patients (54.5 ± 30.1 vs. 30.9 ± 8.4 mg·kg-1·d-1, P = 0.04; and 43.5 ± 20.0 vs. 18.7 ± 7.8 mg·kg-1·d-1, P = 0.04, respectively).

In conclusion, our study shows that patients receiving ART with PI present altered metabolism of the VLDL-IDL-LDL chain compared with patients treated without PI. These data confirm that PI therapy is associated with a physiopathological mechanism for dyslipidemia in addition to the effect of lipodystrophy on lipid metabolism.

Supplementary key words HIV protease inhibitor • nucleoside reverse transcriptase inhibitor • antiretroviral therapy • metabolism abnormalities • apolipoprotein B • dyslipidemia • triglyceride • isotope stable • kinetic study


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