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, 23123 (100%) patients with undetectable HCV-RNA reached success, versus 26134 (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. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

Cento, Valeria;
2015

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, 23123 (100%) patients with undetectable HCV-RNA reached success, versus 26134 (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. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Early response
NS3 protease inhibitors
Viral kinetics
Virological failure
Adult
Antiviral Agents
Drug Therapy, Combination
Female
Hepacivirus
Hepatitis C, Chronic
Humans
Interferon-alpha
Male
Middle Aged
Oligopeptides
Polyethylene Glycols
Prognosis
Proline
RNA, Viral
Ribavirin
Treatment Outcome
Viral Load
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11699/65844
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