title: The safety and efficacy of ledipasvir/sofosbuvir for the treatment of a nosocomial outbreak of HCV in patients with significant cardiovascular disease.
abstract: There is an unmet need for interferon- and ribavirin-free treatment for chronic HCV infection in patients with comorbidities including cardiovascular disease (CVD). The aim of this study was to evaluate the rates of sustained virological response (SVR) and adverse events in a cohort of patients with nosocomially acquired HCV genotype-1b following 12 weeks of therapy with fixed-dose combination (FDC) ledipasvir/sofosbuvir (LDV/SOF).
  
  
  
  This is a prospective, single-centre, open-label study of five non-cirrhotic patients with HCV genotype-1b and significant comorbid CVD, conducted at the Massachusetts General Hospital. All patients were prescribed an FDC tablet (LDV 90 mg/SOF 400 mg) once daily for 12 weeks. Serial measurements of safety parameters, virology, host immune correlates and adherence were performed. The primary outcome was the proportion of patients with SVR (plasma HCV RNA level <25 IU/ml), 12 weeks after treatment completion (SVR12).
  
  
  
  All five patients (100%) achieved SVR12, with no episodes of on- or post-treatment relapse. The most commonly reported adverse events were gastrointestinal illness and upper respiratory viral-type illness. There were no serious adverse events or discontinuations of medication attributable to the study drug. Deep sequencing analysis revealed no baseline NS3, NS5A or NS5B resistance-associated variants.
  
  
  
  In this open-label, uncontrolled, pilot study enrolling patients with HCV genotype-1b and significant CVD, administration of a fixed-dose, oral combination of LDV and SOF for 12 weeks was associated with high rates of SVR and minimal adverse events. Larger prospective studies that also include patients with cirrhosis and prior treatment non-responders are necessary.
authors.affiliation: Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Tracey G
authors.initials: TG
authors.lastname: Simon
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Stamm
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mo
authors.forename: Brian
authors.initials: B
authors.lastname: Doehle
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Jenna
authors.initials: J
authors.lastname: Gustafson
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications*; D003428:Cross Infection / Q000188:drug therapy* / Q000821:virology; D004196:Disease Outbreaks; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D014542:Uridine Monophosphate; D000069474:Sofosbuvir