title: The lopinavir/ritonavir-associated rise in lipids is not related to lopinavir or ritonavir plasma concentration.
abstract: BACKGROUND
  The relationship between lopinavir plasma concentration and the magnitude of lipid elevation after initiation of lopinavir/ritonavir-containing antiretroviral therapy is unclear. The aim of this study was to determine the relationship between drug concentration and lipid changes in two patient cohorts.
  
  
  METHODS
  First, we analysed, in an outpatient cohort, the correlation between percentage lipid changes and lopinavir concentration, measured at least 2 weeks or more after initiation of lopinavir/ritonavir. Second, we analysed the correlation between lipid changes and lopinavir and ritonavir plasma concentrations in antiretroviral-naive patients enrolled in a trial comparing nevirapine plus lopinavir/ritonavir (533/133 mg twice daily) with zidovudine/lamivudine plus lopinavir/ritonavir (400/100 mg twice daily).
  
  
  RESULTS
  In 82 outpatients with 215 lopinavir plasma measurements, we found no significant correlations between lopinavir concentration and changes in lipids a median of 522 days after lopinavir/ritonavir initiation in univariable regression analyses, nor in multivariable analyses adjusting for potential confounders. In 40 trial samples collected 24 months after treatment initiation, the mean (95% CI) percentage increase in low-density lipoprotein cholesterol (LDLc) was significantly greater in the nevirapine/lopinavir/ritonavir group (29.4% [16.8-43.3]) than in the zidovudine/lamivudine/lopinavir/ritonavir group (6.8% [-7.3-23.1]; P=0.03). However, the percentage LDLc change did not correlate with lopinavir or ritonavir concentration ratios (r=-0.25; P=0.17 and r=-0.06; P=0.75). Adding lopinavir or ritonavir concentrations into the multivariable regression analyses did not change the relation between LDLc change and randomized treatment.
  
  
  CONCLUSIONS
  Neither in an HIV outpatient clinic cohort nor in a trial comparing two lopinavir/ritonavir-containing therapies did we find any relation between changes in lipids, and lopinavir and ritonavir concentration, after initiating lopinavir/ritonavir-containing treatment.
authors.affiliation: Department of Internal Medicine, VU University Medical Centre, Amsterdam, the Netherlands. w.f.w.bierman@int.umcg.nl
authors.forename: Wouter F W
authors.initials: WF
authors.lastname: Bierman
authors.forename: Marit G A
authors.initials: MG
authors.lastname: van Vonderen
authors.forename: Agnes I
authors.initials: AI
authors.lastname: Veldkamp
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Sven A
authors.initials: SA
authors.lastname: Danner
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Michiel A
authors.initials: MA
authors.lastname: van Agtmael
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D016208:Databases, Factual; D004338:Drug Combinations; D016903:Drug Monitoring; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000502:physiology; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D061466:Lopinavir / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D019438:Ritonavir / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir