To the Editor:

We read with great interest the articles regarding the treatment of chronic hepatitis C (genotype 1) with the adjunct of telaprevir by McHutchison et al.1 and Hézode et al.2 Although the overall results are encouraging in the setting of a difficult-to-treat disease, our attention was captured by the observation that with telaprevir, a reduced number of patients obtaining a Rapid Virological Response (RVR; i.e., HCV-RNA negative by week 4 of treatment) finally achieved a Sustained Virological Response (SVR). Several studies have in fact demonstrated that when RVR is attained with peginterferon and ribavirin, it predicts SVR in nearly 90% of cases.3–5 On the other hand, when telaprevir is added, the percentage of patients finally achieving SVR is low with respect to the high number of subjects achieving RVR (ranging between 82% and 60%). The only exception has been shown in the PROVE2 trial,2 in which an equal number of patients obtaining RVR and SVR is reported in the group exposed for 24 weeks to peginterferon and ribavirin. This result, however, is in disagreement with the PROVE1 trial,1 in which in the group with an identical treatment schedule, the percentage of patients obtaining SVR with respect to RVR was 75% only. In other words, RVR seems easier to obtain with telaprevir, but less frequently predicts a favorable treatment outcome. A possible explanation might reside in the suboptimal exposure in the majority of telaprevir groups to peginterferon and ribavirin (12 or 24 weeks, instead of the standard 48 weeks); however, it should also be considered that common on-treatment virological predictors might have a different meaning when they are obtained through different pharmacological approaches. As the background of a picture may vary according to the position of either the subject or the photographer, so too when we frame RVR deriving from a different path, we might expect a different perspective. Our observation is not aimed at denoting a possible negative aspect in the use of a promising new drug; instead, we want to underscore the importance of constantly and critically revising the meaning of our on-treatment virological indicators when a new drug is employed. Hopefully, we will all become good photographers.


  1. Top of page
  • 1
    McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 18271838.
  • 2
    Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, et al. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009; 360: 18391850.
  • 3
    Jensen DM, Morgan TR, Marcellin P, Pockros PJ, Reddy KR, Hadziyannis SJ, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy. HEPATOLOGY 2006; 43: 954960.
  • 4
    Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, et al. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. HEPATOLOGY 2008; 47: 4350.
  • 5
    Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. HEPATOLOGY 2008; 47: 18841893.

Leonardo Baiocchi*, Ilaria Lenci*, Marco Carbone*, Mario Angelico*, * Hepatology Unit, Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.