Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects

Jonathan Q. Purnell, Alberto Zambon, Robert H. Knopp, David J. Pizzuti, Ramanuj Achari, John M. Leonard, Charles Locke, John D. Brunzell

Research output: Contribution to journalArticle

330 Scopus citations

Abstract

Background: Intensive therapy of HIV infection with highly active antiretroviral therapy (HAART) dramatically reduces viral loads and improves immune status. Abnormalities of lipid levels, body fat distribution, and insulin resistance have been commonly reported after starting HAART. Whether the lipid abnormalities result from changes in metabolism after an improvement in HIV status or are partly attributable to the effects of protease inhibitor use is unknown. Methods: Twenty-one healthy volunteers participated in a 2 week double-blind, placebo-controlled study on the effect of the protease inhibitor ritonavir on total lipids, apolipoproteins, and post-heparin plasma lipase activities. Results: Those taking ritonavir (n = 11) had significantly higher levels of plasma triglyceride, VLDL cholesterol, IDL cholesterol, apolipoprotein B, and lipoprotein (a) compared with placebo (n = 8). HDL cholesterol was lower with therapy as a result of a reduction in HDL3 cholesterol. Post-heparin lipoprotein lipase (LpL) activity did not change but hepatic lipase activity decreased 20 (P < 0.01) in those taking ritonavirr-compared with placebo. Although all lipoprotein subfractions became triglyceride enriched, most of the increase in triglyceride was in VLDL and not in IDL particles. Conclusion: Treatment with ritonavir in the absence of HIV infection or changes in body composition results in hypertriglyceridemia that is apparently not mediated by impaired LpL activity or the defective removal of remnant lipoproteins, but could be caused by enhanced formation of VLDL. Long-term studies of patients with HIV infection receiving HAART will be necessary to determine the impact of these drugs and associated dyslipidemia on the risk of coronary artery disease. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalAIDS
Volume14
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Apolipoproteins
  • Hepatic lipase
  • Lipids
  • Lipoprotein lipase
  • Ritonavir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Purnell, J. Q., Zambon, A., Knopp, R. H., Pizzuti, D. J., Achari, R., Leonard, J. M., Locke, C., & Brunzell, J. D. (2000). Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects. AIDS, 14(1), 51-57. https://doi.org/10.1097/00002030-200001070-00006