title: Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects.
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 ritonavir-compared with placebo. Although all lipoprotein subfractions became triglyceride enriched, most of the increase in triglyceride was in VLDL and not in IDL particles.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195, USA. purnell@u.washington.edu
authors.forename: J Q
authors.initials: JQ
authors.lastname: Purnell
authors.forename: A
authors.initials: A
authors.lastname: Zambon
authors.forename: R H
authors.initials: RH
authors.lastname: Knopp
authors.forename: D J
authors.initials: DJ
authors.lastname: Pizzuti
authors.forename: R
authors.initials: R
authors.lastname: Achari
authors.forename: J M
authors.initials: JM
authors.lastname: Leonard
authors.forename: C
authors.initials: C
authors.lastname: Locke
authors.forename: J D
authors.initials: JD
authors.lastname: Brunzell
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000097:blood*; D001835:Body Weight / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D010919:Placebos; D019438:Ritonavir / Q000009:adverse effects / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D017320:HIV Protease Inhibitors; D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010919:Placebos; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase; D019438:Ritonavir