Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome

Valeria Cento, Daniele Di Paolo, Domenico Di Carlo, Valeria Micheli, Monica Tontodonati, Francesco De Leonardis, Marianna Aragri, Francesco Paolo Antonucci, Velia Chiara Di Maio, Alessandro Mancon, Ilaria Lenci, Alessandra Manunta, Gloria Taliani, Antonio Di Biagio, Laura Ambra Nicolini, Lorenzo Nosotti, Cesare Sarrecchia, Massimo Siciliano, Simona Landonio, Adriano PellicelliAdriano Gasbarrini, Jacopo Vecchiet, Carlo Federico Magni, Sergio Babudieri, Maria Stella Mura, Massimo Andreoni, Giustino Parruti, Giuliano Rizzardini, Mario Angelico, Carlo Federico Perno, Francesca Ceccherini-Silberstein

Research output: Contribution to journalArticlepeer-review

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. Aims: 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.

Original languageEnglish
Pages (from-to)157-163
Number of pages7
JournalDigestive and Liver Disease
Volume47
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

Keywords

  • Early response
  • NS3 protease inhibitors
  • Viral kinetics
  • Virological failure

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology
  • Medicine(all)

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