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 Petit,Michel Duong,Emmanuel Florentin,Laurence Duvillard,Pascal Chavanet,Jean Marcel Brun,Henri Portier,Philippe Gambert,Bruno Vergès

doi:10.1194/jlr.m300041-jlr200

Jean Michel Petit, Michel Duong + Show 7 more

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https://doi.org/10.1194/jlr.m300041-jlr200

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Abstract

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.

Highlights

The aim of this study was to identify the first abnormalities of apolipoprotein B metabolism in HIVinfected patients treated by antiretroviral therapy (ART) with protease inhibitors (PIs)
To explore the alterations of apolipoprotein B metabolism associated with the direct action of PI therapy, we performed a stable isotope kinetic study of all apoB-containing lipoproteins in HIVinfected patients without lipodystrophy receiving ART with or without HIV PIs
Our results show important alterations of apoB metabolism in patients treated with PIs, with a significantly higher apoB production rate in the VLDL and IDL lipoprotein fractions, leading to increased VLDL-apoB and IDL-apoB plasma pools

Summary

Introduction

The aim of this study was to identify the first abnormalities of apolipoprotein B (apoB) metabolism in HIVinfected patients treated by antiretroviral therapy (ART) with protease inhibitors (PIs). 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.—Petit, J. To explore the alterations of apolipoprotein B (apoB) metabolism associated with the direct action of PI therapy, we performed a stable isotope kinetic study of all apoB-containing lipoproteins in HIVinfected patients without lipodystrophy receiving ART with or without HIV PIs

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