title: Safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with advanced liver disease.
abstract: OBJECTIVE
  There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease.
  
  
  METHODS
  Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C.
  
  
  RESULTS
  Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9).
  
  
  CONCLUSIONS
  The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability.
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, IRYCIS, Madrid, Spain. jcasado.hrc@salud.madrid.org
authors.forename: José L
authors.initials: JL
authors.lastname: Casado
authors.forename: María
authors.initials: M
authors.lastname: Del Palacio
authors.forename: Javier
authors.initials: J
authors.lastname: Moya
authors.forename: José M
authors.initials: JM
authors.lastname: Rodriguez
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno
authors.forename: María J
authors.initials: MJ
authors.lastname: Perez-Elías
authors.forename: Ana
authors.initials: A
authors.lastname: Belso
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D061466:Lopinavir