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* * PegIFN, peginterferon; RBV, ribavirin. We performed a pilot study to try to answer this question. In this study, difficult-to-treat US patients, namely those with genotype?1 infection, HCV RNA 850,000?IU/mL, and body weight 85?kg, were randomized to a standard regimen of peginterferon alfa-2a 180?μg/wk plus ribavirin 1200?mg/day or to 1 of 3 more intense regimens. In the most intensive regimen, patients received peginterferon alfa-2a 270?μg/wk plus ribavirin 1600?mg/day, and the remaining 2 arms contained either the higher dose of ribavirin or the higher dose of peginterferon alfa-2a, combined with the lower dose of the other agent. Thus, this 4-arm study allowed us to investigate the impact of both changes to peginterferon and changes to ribavirin dosing in this difficult-to-treat group. * cEVR, complete early virologic response; PegIFN, peginterferon; RBV, ribavirin; RVR, rapid virologic response; SVR, sustained virologic response. This slide shows that patients receiving the most intensive regimen had a 13% chance of achieving RVR vs only 2% for those who were treated with the standard regimen. At Weeks?12, 24, and 48, the differences were not as pronounced, but the SVR rate—measured 6 months after stopping treatment or at Week?72—was higher in patients treated with the most intensive regimen vs those treated with the standard regimen: 47% vs 28%, respectively. However, this study was not powered to show differences in SVR rates, and the focus was on the early viral kinetic responses. Nevertheless, there clearly was an indication that a more intensive regimen might overcome some of the aforementioned treatment-resistant characteristics. * PegIFN, peginterferon; RBV, ribavirin. Interestingly, these regimens appeared to greatly impact relapse rates. In fact, the relapse rate for the group that was treated with the most intensive regimen was less than 50% of those who were treated with other regimens. These preliminary results are being tested in a muc