title: Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome.
abstract: BACKGROUND
  Triple therapy with telaprevir/boceprevir + pegylated-interferon+ribavirin can achieve excellent antiviral efficacy, but it can be burdened with resistance development at failure.
  
  
  OBJECTIVE
  To evaluate kinetics of hepatitis C virus (HCV) RNA decay and early resistance development, in order to promptly identify patients at highest risk of failure to first generation protease inhibitors.
  
  
  METHODS
  HCV-RNA was prospectively quantified in 158 patients receiving pegylated-interferon+ribavirin+telaprevir (N = 114) or+boceprevir (N = 44), at early time-points and during per protocol follow-up. Drug resistance was contextually evaluated by population sequencing.
  
  
  RESULTS
  HCV-RNA at week-2 was significantly higher in patients experiencing virological failure to triple-therapy than in patients with sustained viral response (2.3 [1.9-2.8] versus 1.2 [0.3-1.7]log IU/mL, p < 0.001). A 100 IU/mL cut-off value for week-2 HCV-RNA had the highest sensitivity (86%) in predicting virological success. Indeed, 23/23 (100%) patients with undetectable HCV-RNA reached success, versus 26/34 (76.5%) patients with HCV-RNA<100 IU/mL, and only 11/31 (35.5%) with HCV-RNA > 100 IU/mL (p < 0.001). Furthermore, differently from failing patients, none of the patient with undetectable HCV-RNA at week-2 had baseline/early resistance.
  
  
  CONCLUSIONS
  With triple therapy based on first generation protease inhibitors, suboptimal HCV-RNA decay at week-2 combined with early detection of resistance can help identifying patients with higher risk of virological failure, thus requiring a closer monitoring during therapy.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cento
authors.affiliation: Hepatology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Paolo
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Di Carlo
authors.affiliation: Unit of Microbiology, Hospital Sacco of Milan, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Micheli
authors.affiliation: Infectious Disease Clinic, Chieti, Italy; Infectious Disease Unit, Pescara General Hospital, Pescara, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Tontodonati
authors.affiliation: Hepatology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Leonardis
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Aragri
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Antonucci
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Velia Chiara
authors.initials: VC
authors.lastname: Di Maio
authors.affiliation: Unit of Microbiology, Hospital Sacco of Milan, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mancon
authors.affiliation: Hepatology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lenci
authors.affiliation: Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Manunta
authors.affiliation: "La Sapienza" University, Rome, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.affiliation: S. Martino Hospital, Genova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.affiliation: S. Martino Hospital, Genova, Italy.
authors.forename: Laura Ambra
authors.initials: LA
authors.lastname: Nicolini
authors.affiliation: Hepatology Unit, National Institute of Health, Migration and Poverty, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Nosotti
authors.affiliation: Infectious Disease, University Hospital of Rome "Tor Vergata", Rome, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Sarrecchia
authors.affiliation: Gastroenterology, Catholic University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Siciliano
authors.affiliation: Division of Infectious Disease, Hospital Sacco of Milan, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Landonio
authors.affiliation: Hepatology Unit, San Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Pellicelli
authors.affiliation: Gastroenterology, Catholic University of Rome, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Gasbarrini
authors.affiliation: Infectious Disease Clinic, Chieti, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Vecchiet
authors.affiliation: Division of Infectious Disease, Hospital Sacco of Milan, Milan, Italy.
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Magni
authors.affiliation: Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Babudieri
authors.affiliation: Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Italy.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Mura
authors.affiliation: Infectious Disease, University Hospital of Rome "Tor Vergata", Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
authors.affiliation: Infectious Disease Unit, Pescara General Hospital, Pescara, Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Parruti
authors.affiliation: Division of Infectious Disease, Hospital Sacco of Milan, Milan, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.affiliation: Hepatology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy. Electronic address: ceccherini@med.uniroma2.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011379:Prognosis; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011092:Polyethylene Glycols; D012254:Ribavirin; 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; D011392:Proline
keywords: Early response; NS3 protease inhibitors; Viral kinetics; Virological failure