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. 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 versus 26/34 (76.5%) patients with HCV-RNA   100 IU/mL ( p 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.