title: Fosamprenavir/ritonavir in patients with viral hepatitis coinfection: an observational multicohort study.
abstract: Safety and tolerability evaluation of adapted dose regimens containing fosamprenavir/ritonavir (FPV/r) in HIV-infected subjects with viral hepatitis co-infection.
  
  
  
  A retrospective multicohort analysis was conducted. Subjects from three European cohorts who started FPV/r or lopinavir/ritonavir (LPV/r) as a comparator contributed data to a centralized database. Subjects were divided into five groups by treatment regimen and level of hepatic impairment (aspartate aminotransferase [AST] platelet ratio index [APRI] score < or ≥2). Multivariable Cox regression analyses controlling for demographic factors, baseline CD4 count, FIB-4 score, use of antiretroviral therapy, and laboratory markers (bilirubin and platelet count) were performed to identify factors independently associated with risk of developing adverse events or safety events (eg, drug discontinuation, alanine aminotransferase (ALT) elevation, hepatic decompensation/death).
  
  
  
  A total of 1096 patients contributed data to the study. Fosamprenavir/ritonavir (except in subjects with APRI ≥2 receiving standard dose) was associated with a higher two-year risk of drug discontinuation compared with LPV/r. Restricting the analysis to discontinuations due to adverse events (AEs), only subjects who received the reduced dose were more likely to discontinue ≥1 drug in the FPV/r regimen. There were no statistical differences in ALT elevation between groups. Incidence of hepatic decompensation events was similar among groups except for subjects who received non standard doses of FPV, though the number of events was small.
  
  
  
  Fosamprenavir/ritonavir discontinuation rate due to AEs or ALT elevation was similar across all European-approved FPV/r doses and to that of LPV/r subjects.  Although liver tolerated antiretrovirals, such as integrase inhibitor and entry inhibitor, the use of FPV/r is acceptable in HIV infected patients with viral hepatitis.
authors.affiliation: a University Division of Infectious and Tropical Diseases , University of Brescia and Spedali Civili General Hospital, Spedali Civili Hospital , Brescia , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Nasta
authors.affiliation: b Service des Maladies Infectieuses et Tropicales, Hôpital Cochin , APHP-Université Paris Descartes , Paris , France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: c Infectious Diseases Unit, Department of Health Sciences , ASST Santi Paolo e Carlo University Hospital , Milan , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.affiliation: d Worldwide Epidemiology , GlaxoSmithKline , Stockley Park , UK.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Pimenta
authors.affiliation: a University Division of Infectious and Tropical Diseases , University of Brescia and Spedali Civili General Hospital, Spedali Civili Hospital , Brescia , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cerini
authors.affiliation: a University Division of Infectious and Tropical Diseases , University of Brescia and Spedali Civili General Hospital, Spedali Civili Hospital , Brescia , Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Giralda
authors.affiliation: e ISPED , Université Bordeaux , F33000 Bordeaux , France.|f INSERM, Centre INSERM U897 , Bordeaux , France.
authors.forename: Maria
authors.initials: M
authors.lastname: Winnock
authors.affiliation: g Research Department of Infection and Population Health , University College London , London , UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects; D002423:Cause of Death; D060085:Coinfection; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006505:Hepatitis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; D019438:Ritonavir; C426859:fosamprenavir
keywords: Fosamprenavir; HCV; HIV; Hepatic impairment; Lopinavir; Viral hepatitis