title: Liver toxicity of antiretroviral combinations including fosamprenavir plus ritonavir 1400/100 mg once daily in HIV/hepatitis C virus-coinfected patients.
abstract: Abstract Our objective was to evaluate the liver toxicity of antiretroviral regimens including fosamprenavir plus ritonavir (FPV/r) 1400/100 mg once daily (QD) in HIV/hepatitis C virus (HCV)-coinfected patients. This was a prospective cohort study that included 117 HIV/HCV-coinfected patients who started FPV/r 1400/100 mg QD-based antiretroviral therapy (ART) and who neither had received a previous antiretroviral regimen containing FPV nor had a past history of virologic failure while receiving protease inhibitors (PI). The primary end point of the study was the occurrence of grade 3-4 liver enzymes elevations (LEE) within 1 year after starting FPV/r QD. Factors potentially associated with grade 3-4 LEE, including baseline liver fibrosis, were analyzed. Eleven (9%) patients had a grade 3-4 LEE during the follow-up, resulting in an incidence of severe liver toxicity of 9% (95% confidence interval 4.1-14.6%). None of these cases led to FPV/r discontinuation. Baseline liver fibrosis could be assessed in 97 (83%) patients. Six of 71 patients (8%) with significant fibrosis had a grade 3-4 LEE versus 2 of 26 (8%) without significant fibrosis (p=1.0). Twenty (21%) patients had cirrhosis at baseline. There were no cases of LEE among cirrhotics. In conclusion, the incidence of severe liver toxicity after 1 year of therapy with FPV/r QD-based ART in HIV/HCV-coinfected patients is similar to what has been reported with other boosted PIs. In addition, the presence of significant fibrosis or cirrhosis was not associated with the emergence of liver toxicity. Thus, ART regimens containing FPV/r QD may be considered safe in HIV/HCV-coinfected patients, including those with cirrhosis.
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Merchante
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.forename: Marcial
authors.initials: M
authors.lastname: Delgado-Fernández
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ríos-Villegas
authors.forename: Manuel
authors.initials: M
authors.lastname: Márquez-Solero
authors.forename: Dolores
authors.initials: D
authors.lastname: Merino
authors.forename: Juan
authors.initials: J
authors.lastname: Pasquau
authors.forename: Carolina
authors.initials: C
authors.lastname: García-Figueras
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Martínez-Pérez
authors.forename: Mohamed
authors.initials: M
authors.lastname: Omar
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.forename: Rosario
authors.initials: R
authors.lastname: Mata
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; C426859:fosamprenavir