title: Favorable adverse event profile of sofosbuvir/ribavirin compared to boceprevir/interferon/ribavirin for treatment of hepatitis C.
abstract: BACKGROUND
  Triple therapy for the treatment of hepatitis C virus (HCV) with first-generation directly acting antiviral agents, the non-structural serine protease inhibitors boceprevir (BOC) and telaprevir have resulted in improved sustained virologic response (SVR) rates. However, a high incidence of adverse events (AEs), high pill burdens and drug interactions remain significant barriers to successful completion of therapy. The aim of this study was to evaluate the AEs observed with BOC triple therapy in comparison to IFN-free sofosbuvir/ribavirin (SOF/RBV) therapy in HCV monoinfected, genotype-1 (GT-1) individuals.
  
  
  METHODS
  We retrospectively evaluated HCV monoinfected, treatment-naïve or -experienced, GT-1 individuals treated with either BOC/IFN/RBV at the Veterans Affairs Medical Center, Baltimore (n = 97) or SOF/RBV in the NIAID SPARE clinical trial (n = 60). AEs, namely hematologic (hemoglobin, neutrophil and platelet counts), hepatic (alanine transaminase or bilirubin) and renal (eGFR), were measured according to the DAIDS toxicity table (version 1.0).
  
  
  RESULTS
  BOC/IFN/RBV was associated with significantly more AEs, most commonly neutropenia, anemia and thrombocytopenia. In the SOF/RBV cohort, five (8 %) patients discontinued treatment early, but none (0 %) were because of AEs, while 60 (62 %) patients on triple therapy discontinued treatment early, 34 (57 %) because of AEs. SVR24 rates were 68 versus 34 % with SOF/RBV versus BOC/IFN/RBV.
  
  
  CONCLUSIONS
  SOF/RBV treatment was associated with fewer side effects than BOC-based triple therapy, appearing to be a safer and more tolerable alternative for HCV GT-1 subjects. These results show that emerging IFN-free therapies may enhance patient adherence, allowing treatment of larger number of patients with improved efficacy.
authors.affiliation: Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Townsend
authors.affiliation: Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Macharia
authors.affiliation: Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Majid
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Nelson
authors.affiliation: Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Redfield
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA. skottilil@niaid.nih.gov.
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.affiliation: Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Talwani
authors.affiliation: Division of Infectious Diseases, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.|Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N204, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
keywords: Adverse events; HCV monoinfection; Ribavirin; Sofosbuvir