title: Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus: 144-week results from a randomized, placebo-controlled trial.
abstract: In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 coinfected with HBV and/or HCV, maraviroc-containing treatment regimens were not associated with increased hepatotoxicity.
  
  
  
  In this randomized, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (Clinicaltrials.gov identifier, NCT01327547). The primary end point was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary end points included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography and an optional biopsy substudy.
  
  
  
  Through 144 weeks of treatment, two (maraviroc) and three (placebo) patients met the protocol-defined Grade 3/4 ALT end point. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on maraviroc) showed signs of decreased fibrosis. One (maraviroc) and two (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs versus three in the placebo group. One death in the maraviroc group and two deaths in the placebo group were reported.
  
  
  
  Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.
authors.affiliation: Department of Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Juergen K
authors.initials: JK
authors.lastname: Rockstroh
authors.affiliation: Global Clinical Development, Pfizer Inc., Collegeville, PA, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Plonski
authors.affiliation: Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Bansal
authors.affiliation: Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA.|Department of Medicine, Division of Infectious Diseases, New York Medical College, Valhalla, NY, USA.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Small
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.affiliation: Maladies Infectieuses et Tropicales, Hôpital Tenon, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.affiliation: Safety Evaluation and Risk Management, GlaxoSmithKline, London, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Zhang-Roper
authors.affiliation: Clinical Sciences, Pfizer Inc., Groton, CT, USA.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Wang
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario de Valme, Instituto de Investigación Biomédica de Sevilla (IBIS), Seville, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Clinical Sciences, Pfizer Inc., Groton, CT, USA.
authors.forename: Jayvant
authors.initials: J
authors.lastname: Heera
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D060085:Coinfection; D003510:Cyclohexanes / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D023581:HIV Fusion Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006509:Hepatitis B / Q000821:virology; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008111:Liver Function Tests; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D014230:Triazoles; D000077592:Maraviroc