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.
Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome / V. Cento, D. Di Paolo, D. Di Carlo, V. Micheli, M. Tontodonati, F. De Leonardis, M. Aragri, F.P. Antonucci, V.C. Di Maio, A. Mancon, I. Lenci, A. Manunta, G. Taliani, A. Di Biagio, L.A. Nicolini, L. Nosotti, C. Sarrecchia, M. Siciliano, S. Landonio, A. Pellicelli, A. Gasbarrini, J. Vecchiet, C.F. Magni, S. Babudieri, M.S. Mura, M. Andreoni, G. Parruti, G. Rizzardini, M. Angelico, C.F. Perno, F. Ceccherini-Silberstein. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - 47:2(2015 Feb), pp. 157-163. [10.1016/j.dld.2014.11.010]
Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome
V. CentoPrimo
;D. Di Carlo;V. Micheli;A. Mancon;C.F. Perno;
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.File | Dimensione | Formato | |
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