According to the recently released American Association for the Study of Liver Diseases (AASLD) guidelines for the treatment of hepatitis C virus (HCV) genotype 1 chronic infection, 1 in treatment-naı ¨ve subjects the association of boceprevir or telaprevir with peginterferon-alpha and ribavirin is strongly recommended as the optimal therapy. In patients treated with boceprevir, peginterferon, and ribavirin, a response-guided treatment schedule was established at week 8, through the assessment of HCV RNA level, making feasible a shortened duration of treatment (i.e., 28 weeks) in the case of undetectable viral replication. In this regard, we believe that the choice of 8 weeks for the definition of treatment duration needs some comment. The phase 2 and 3 clinical trials with boceprevir 2,3 featured the use of peginterferon-ribavirin for 4 weeks (the lead-in period) before boceprevir was added. The reasons for starting with a lead-in phase would be to lower HCV-RNA before exposure to a protease inhibitor in order to reduce the risk of resistance and viral breakthrough. 2 However, in the studies mentioned the achievement of virologic response after the lead-in therapy (4 weeks) was shown to be highly effective for the prediction of sustained virologic response (SVR; HCV-RNA undetectability leading to SVR in a percentage of patients between 89% and 100%, independently from the treatment arm). 2,3 Indeed, Poordad et al. 3 stated that in patients with undetectable HCV RNA levels after the lead-in period, boceprevir administration would not result in a higher rate of SVR than that obtained with the use of standard therapy. Therefore, the lead-in period as well as interleukin (IL)-28B genotype assessment might be used to better define the eligible patients for peginterferon introduction, thus avoiding their possible overuse with additional costs and side effects. In our opinion, it seems to be reasonable to reconsider the assessment of HCV-RNA at week 4 (end of lead-in) in the response-guided treatment guidelines of naı ¨ve genotype-1-infected patients.