title: Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies.
abstract: BACKGROUND
  The development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and define the most appropriate retreatment, it is important to distinguish virologic relapse from reinfection when patients in whom HCV is eradicated during treatment become infected with a new HCV strain after treatment.
  
  
  METHODS
  We investigated the prevalence of late recurrent viremia (patients with sustained virologic response 12 weeks after the end of treatment but detectable HCV RNA at follow-up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish virologic relapse from reinfection.
  
  
  RESULTS
  Across 11 phase 3 clinical trials of ledipasvir-sofosbuvir (SOF) and SOF, only 12 of 3004 patients had detectable HCV RNA following sustained virologic response 12 weeks after the end of treatment. Of these 12 patients with late recurrent viremia, 11 had the same HCV genotype/subtype at baseline and at recurrence. Phylogenetic analysis demonstrated that 58% (7 of 12) of these patients were successfully treated with the SOF-based regimen, with HCV eradication achieved, but became reinfected with a different HCV strain after treatment. The remaining 5 patients with late recurrent viremia had virologic relapse in which the HCV present at baseline persisted in the liver or another compartment and reemerged in the blood 24 weeks after treatment.
  
  
  CONCLUSIONS
  The incidence of late recurrent viremia was low. Distinguishing reinfection from virologic relapse has implications for determining true treatment efficiency and selecting optimal retreatment strategies.
authors.affiliation: J. W. Goethe University Hospital, Frankfurt am Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Institute of Nutrition, Moscow, Russia.
authors.forename: Vasily
authors.initials: V
authors.lastname: Isakov
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Evguenia S
authors.initials: ES
authors.lastname: Svarovskaia
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hedskog
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Ross
authors.initials: R
authors.lastname: Martin
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chodavarapu
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mo
authors.affiliation: University of Paris Diderot and Saint-Louis Hospital, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology*; D006801:Humans; D008297:Male; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral; D012008:Recurrence; D019233:Retreatment; D017422:Sequence Analysis, DNA; D000069474:Sofosbuvir / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014766:Viremia / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D000069474:Sofosbuvir; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: hepatitis C virus; late recurrent viremia; reinfection; sustained virologic response; viologic relapse