title: Dynamic changes in HCV RNA levels and viral quasispecies in a patient with chronic hepatitis C after telaprevir-based treatment.
abstract: BACKGROUND
  Telaprevir is a selective inhibitor of the hepatitis C virus NS3·4A serine protease. Treatment with telaprevir resulted in a rapid HCV-RNA decline in chronic hepatitis C genotype 1 patients.
  
  
  OBJECTIVE
  To report the clinical and viral course of a patient treated with telaprevir in combination with pegylated interferon-alpha-2a and ribavirin in a Phase 2 clinical trial (PROVE3).
  
  
  METHODS
  This previous non-responder to interferon based therapy was treated for 40 weeks with a telaprevir, pegylated interferon alpha-2a, and ribavirin regimen. Viral sequencing and phylogenetic analysis were performed before, during and after therapy.
  
  
  RESULTS
  The patient, a 54 years old male patient, experienced a viral relapse 4 weeks post-treatment and HCV-RNA levels continued to increase 14 weeks post-treatment (150,000 IU/mL). The viral population, which was wild type at baseline, consisted of only V36A variants at both of these post-treatment timepoints. Subsequently, this patient had a transient disappearance of HCV-RNA for more than 1 year in the absence of antiviral therapy. Thereafter, HCV-RNA reappeared again with a viral population consisting of only wild type virus. Phylogenetic analysis of NS3·4A corresponded with a viral population bottleneck resulting in changes in viral quasispecies.
  
  
  CONCLUSIONS
  In this case report, significant viral load reductions resulted in a genetic bottleneck leading to a reduction of variability in the hepatitis C viral population. We hypothesize that the reduction in viral heterogeneity potentially led to a reduced viral capacity to adapt to a host immune response leading to a transient loss of detectable HCV-RNA.
authors.affiliation: Academic Medical Center, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands. j.debruijne@amc.nl
authors.forename: Joep
authors.initials: J
authors.lastname: de Bruijne
authors.forename: James C
authors.initials: JC
authors.lastname: Sullivan
authors.forename: Tara L
authors.initials: TL
authors.lastname: Kieffer
authors.forename: Martyn
authors.initials: M
authors.lastname: Botfield
authors.forename: Ben
authors.initials: B
authors.lastname: Shames
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
authors.forename: Richard
authors.initials: R
authors.lastname: Molenkamp
authors.forename: Christine
authors.initials: C
authors.lastname: Weegink
authors.forename: Henk
authors.initials: H
authors.lastname: Reesink
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a