7th Conference on Retroviruses and Opportunistic Infections


San Francisco, CA - January 30 -February 4, 2000



NELFINAVIR AND RITONAVIR STIMULATE TRIGLYCERIDE PRODUCTION IN HEPATIC CELLS.

Conf Retroviruses Opportunistic Infect 2000 Jan 30-Feb 2; 7:82 (abstract no. 39)

D. Winegar, B. Koszalka, And J. Lenhard
Glaxo Wellcome Inc., Res. Triangle Park, NC.

OBJECTIVE: To determine the effects of HIV protease inhibitors on the synthesis and secretion of lipids in the human hepatoma cell line HepG2.

METHODS: HepG2 cells were treated for 24 hrs with varying doses (0.1-10 µM) of amprenavir, indinavir, nelfinavir, saquinavir and ritonavir. Cells were then labeled with [14C]acetate and the incorporation of radiolabel into cellular and secreted fatty acids, triglycerides, cholesterol and cholesteryl esters was determined by HPLC analysis.

RESULTS: Nelfinavir produced a concentration-dependent increase in the synthesis and secretion of triglycerides derived from [14C]acetate (maximal 2.5-fold increase in cellular triglycerides at 10 µM nelfinavir). Synthesis of fatty acids, cholesterol and cholesteryl esters remained unchanged. Ritonavir showed a similar, but somewhat weaker effect, increasing triglyceride synthesis 38% at 10 µM. amprenavir, indinavir and saquinavir had no effect on lipid synthesis.

CONCLUSION: Treatment with certain HIV protease inhibitors is often accompanied by elevations in serum triglycerides and cholesterol. Among the drugs used, ritonavir, the combination ritonavir/saquinavir and nelfinavir are often associated with increases in both triglyceride and cholesterol levels. In HepG2 cells, ritonavir and nelfinavir significantly increased the synthesis and secretion of triglycerides. Stimulation of triglyceride synthesis and secretion in hepatic cells may, in part, explain the elevation in serum triglycerides observed with protease inhibitor therapy.

Keywords: AEGIS, Nelfinavir, Ritonavir, Saquinavir, HIV Protease Inhibitors, Indinavir, Triglycerides, Cholesterol, Chromatography, High Pressure Liquid, Sulfonamides, Reverse Transcriptase Inhibitors, Fatty Acids, Cholesterol Esters, Blood Chemical Analysis, VX 478, Human, AIDS

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2000-01-30
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Copyright © 2000 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.