title: Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3.
abstract: OBJECTIVE
  To examine the antiviral activity of boceprevir, a hepatitis C virus (HCV) protease inhibitor, in HCV genotype (G) 2/3-infected patients.
  
  
  METHODS
  We assessed boceprevir and telaprevir activity against an HCV G2 and G3 isolates enzyme panel, in replicon, and in phenotypic cell-based assays. Additionally, a phase I study evaluated the antiviral activity of boceprevir monotherapy (200mg BID, 400mg BID, or 400mg TID) vs. placebo for 14 days in HCV G2/3 treatment-naive patients.
  
  
  RESULTS
  Boceprevir and telaprevir similarly inhibited G1 and G2 NS3/4A enzymes and replication in G1 and G2 replicon and cell-based assays. However, telaprevir demonstrated lower potency than boceprevir against HCV G3a enzyme (Ki=75 nM vs. 17 nM), in the G3a replicon assay (EC₅₀=953 nM vs. 159 nM), and against HCV G3a NS3 isolates (IC₅₀=3312 nM vs. 803 nM) in the cell-based assay. In HCV G2/3-infected patients, boceprevir (400 mg TID) resulted in a maximum mean decrease in HCV RNA of -1.60 log vs. -0.21 log with placebo.
  
  
  CONCLUSIONS
  In vitro, boceprevir is more active than telaprevir against the HCV G3 NS3/4A enzyme in cell-based and biochemical assays and against G3 isolates in replicon assays. In HCV G2/3-infected treatment-naive patients, decreases in HCV RNA levels with boceprevir (400 mg TID) were comparable to those observed with the same dose in HCV treatment-experienced G1-infected patients.
authors: Hospital Universitario Austral, Pilar, Argentina. msilva@cas.austral.edu.ar
authors: Marcelo O
authors: MO
authors: Silva
authors: Michelle
authors: M
authors: Treitel
authors: Donald J
authors: DJ
authors: Graham
authors: Stephanie
authors: S
authors: Curry
authors: Maria J
authors: MJ
authors: Frontera
authors: Patricia
authors: P
authors: McMonagle
authors: Samir
authors: S
authors: Gupta
authors: Eric
authors: E
authors: Hughes
authors: Robert
authors: R
authors: Chase
authors: Fred
authors: F
authors: Lahser
authors: Richard J O
authors: RJ
authors: Barnard
authors: Anita Y M
authors: AY
authors: Howe
authors: John A
authors: JA
authors: Howe
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012093:Replicon / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011392:Proline; D011480:Protease Inhibitors; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C080107:NS4B protein, flavivirus; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide