title: Lopinavir/ritonavir pharmacokinetics, efficacy, and safety in HIV and hepatitis B or C coinfected adults without symptoms of hepatic impairment.
abstract: OBJECTIVE
  Lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors is one standard antiretroviral therapy regimen, both in patients with HIV alone and coinfected with hepatitis B or C. Our objective was to investigate whether hepatitis coinfection without clinical signs of hepatic impairment is a cofactor altering lopinavir pharmacokinetics and influencing therapy outcome.
  
  
  METHODS
  Steady-state 12-hour pharmacokinetic profiles of lopinavir/ritonavir were assessed in patients with (group 1, n = 20) or without (group 2, n = 36) hepatitis coinfection, taking lopinavir/ritonavir 400/100 mg twice a day plus nucleoside reverse transcriptase inhibitors, measured by means of high-performance liquid chromatography-tandem mass spectrometry. Demographic (sex, age, weight), pharmacological (formulation, comedication), clinical, and virological/immunologic parameters (HIV-RNA PCR, CD4(+) cell count) were compared between the groups and included in regression analyses for correlations with lopinavir pharmacokinetic parameters (C(min), C(max), AUC, CL, and t(1/2)) and viral load evolution over 48 weeks on therapy. Patient pairs were matched 1:2 for the parameters sex, age, weight, ethnicity, and drug formulation.
  
  
  RESULTS
  None of the hepatitis-related cofactors (aspartate aminotransferase, alanine aminotransferase, γGT, HBe Ag, HBsAg, HCV-RNA PCR, HCV-therapy) had an influence on lopinavir pharmacokinetics in this group of patients. Lopinavir C(min) (P = 0.039) and area under the curve (P = 0.038) and ritonavir C(max) (P = 0.049) were significantly enhanced in hepatitis-coinfected patients, but correlated only with drug formulation (ie, soft gel capsule or Meltrex tablet formulation, multivariate regression analysis, P = 0.001), not hepatitis coinfection.
  
  
  CONCLUSIONS
  Despite moderately enhanced lopinavir/ritonavir plasma concentrations, regular therapeutic drug monitoring is not to be considered in hepatitis-coinfected patients without hepatic impairment. Antiviral efficacy is comparable between both groups, a less-pronounced CD4(+) cell increase in hepatitis-coinfected patients is in line with previously published data.
authors.affiliation: *HIVCENTER, Department of Internal Medicine II, and †Institute of Medical Virology, Hospital of the Johann Wolfgang Goethe University, Frankfurt; and ‡HIV-Laboratory, Therapia GmbH, c/o Auguste Viktoria Hospital, Berlin, Germany.
authors.forename: Pavel
authors.initials: P
authors.lastname: Khaykin
authors.forename: Peter
authors.initials: P
authors.lastname: Kotzerke
authors.forename: Christoph
authors.initials: C
authors.lastname: Stephan
authors.forename: Gabi
authors.initials: G
authors.lastname: Nisius
authors.forename: Markus
authors.initials: M
authors.lastname: Bickel
authors.forename: Annette
authors.initials: A
authors.lastname: Haberl
authors.forename: Martin
authors.initials: M
authors.lastname: Stürmer
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
authors.forename: Reinhard
authors.initials: R
authors.lastname: Brodt
authors.forename: Nils
authors.initials: N
authors.lastname: von Hentig
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002626:Chemistry, Pharmaceutical; D060085:Coinfection / Q000188:drug therapy; D004338:Drug Combinations; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008099:Liver / Q000187:drug effects; D061466:Lopinavir / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D061466:Lopinavir; D019438:Ritonavir