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

• Published in: Digestive and liver disease Vol. 47; no. 2; pp. 157 - 163
• Main Authors: Cento, Valeria, Di Paolo, Daniele, Di Carlo, Domenico, Micheli, Valeria, Tontodonati, Monica, De Leonardis, Francesco, Aragri, Marianna, Antonucci, Francesco Paolo, Di Maio, Velia Chiara, Mancon, Alessandro, Lenci, Ilaria, Manunta, Alessandra, Taliani, Gloria, Di Biagio, Antonio, Nicolini, Laura Ambra, Nosotti, Lorenzo, Sarrecchia, Cesare, Siciliano, Massimo, Landonio, Simona, Pellicelli, Adriano, Gasbarrini, Adriano, Vecchiet, Jacopo, Magni, Carlo Federico, Babudieri, Sergio, Mura, Maria Stella, Andreoni, Massimo, Parruti, Giustino, Rizzardini, Giuliano, Angelico, Mario, Perno, Carlo Federico, Ceccherini-Silberstein, Francesca
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2015
• Subjects: Adult; Antiviral Agents - therapeutic use; Drug Therapy, Combination; Early response; Female; Gastroenterology and Hepatology; Hepacivirus - genetics; Hepatitis C, Chronic - blood; Hepatitis C, Chronic - drug therapy; Humans; Interferon-alpha - therapeutic use; Male; Middle Aged; NS3 protease inhibitors; Oligopeptides - therapeutic use; Polyethylene Glycols - therapeutic use; Prognosis; Proline - analogs & derivatives; Proline - therapeutic use; Ribavirin - therapeutic use; RNA, Viral - blood; Treatment Outcome; Viral kinetics; Viral Load; Virological failure; Virological failure; Early response; NS3 protease inhibitors; Viral kinetics
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2014.11.010

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.