Characterization of nonrapid virologic response patients infected with HCV genotype 1 who may relapse after standard therapy with peginterferon plus ribavirin

Approximately 50% of patients with hepatitis C virus (HCV) genotype 1 treated with peginterferon alfa-2a/ribavirin discontinue treatment early or experience a suboptimal response despite 48 weeks of therapy. The objective of this analysis was to develop a model to identify nonrapid virologic response (non-RVR) patients who may be candidates for intensified therapy that would increase treatment response. The retrospective analysis included non-RVR patients from four trials of 48-week peginterferon alfa-2a/ribavirin treatment. Patients were grouped into those who cleared virus between weeks 5 and 12 (complete early virologic responders, cEVR) or between weeks 13 and 24 (slow responders). A model was developed to predict relapse at the end of follow-up (week 72). An optimal model was evaluated and compared with current practice by using receiver operating characteristic curves, sensitivity and specificity. In total, 539 non-RVR patients were eligible for analysis of which 72% experienced cEVR and 28% were slow responders. Variables associated with relapse included age, ethnicity, baseline HCV RNA and interval of time to HCV RNA undetectable. The optimal model was most accurate at predicting patients at risk for relapse. The practice of considering treatment intensification (e.g. extending treatment duration) in all slow responders was less accurate but likely most practical. A week 4 HCV <2-log reduction was the earliest but least accurate marker. We developed a model that could identify non-RVR patients at high risk for relapse after 48 weeks of peginterferon alfa-2a plus ribavirin and who may benefit from intensified therapy to reduce this risk of relapse.