Background:  Therapy with pegylated interferon (pegINF) and ribavirin (RBV) achieves lower sustained viral response rates in patients (patients) co-infected with HIV and hepatitis C virus (HCV) compared with those with HCV alone. The aim of this prospective randomized controlled trial was to test the hypothesis that the sustained viral response rate would be higher in co-infected patients treated for longer duration (72 weeks) compared to the standard (48 weeks)

Methods:  Initially, all patients received pegINFa-2b (1.5 mg /kg) weekly plus weight-based RBV (800 to 1400 mg/day) for 24 weeks. Patients with no HCV RNA detected at week 24 (<600 IU/mL) were randomized to standard (group A, 48 weeks) or extended (group B, 72 weeks) duration of therapy. Growth factors were permitted. Primary outcome measure was sustained viral response rate; secondary endpoints were early viral response rate and incidence of adverse events. Sustained viral response was compared between groups using the c² test. Predictors of sustained viral response were assessed by multivariate logistic regression.

Results:  We enrolled 177 patients at 21 community and academic U.S. sites. Baseline characteristics:  male 69%; black 41%; mean age 45 years (SD 6.77); ART 78%; HCV genotype 1, 80%; median HCV RNA level, 600,000 IU/mL (IQR 500,000 to 1,738,642); elevated ALT, 76%; CD4 >200 cells/mm³, 94%; HIV RNA <400 copies/mL, 65%. Overall, by intention-to-treat analysis:  week 12 early viral response, 43% (76 of 177); week 24 undetectable HCV RNA, 34.5% (61 of 177). At week 24, 61 were randomized to standard or extended duration. The sustained viral response rate was similar in both groups:  A, 50% (15 of 30); B, 54.8% (17 of 31)(p = 0.7). However, 52.5% of patients randomized at week 24 did not complete the assigned treatment duration (adverse events, 6 patients; declined extended duration, 21 patients). Among all enrolled subjects the sustained viral response rate was:  genotype 1 12.8% (18 of 141), genotype non-1, 47.2% (17 of 36). Therapy was discontinued in 35 patients (20%) due to adverse events. Erythropoietin was used in 70 patients (40 %). On univariate analysis, early viral response, genotype non-1, Caucasian race, and use of erythropoietin were significant positive predictors of sustained viral response; on logistic regression only early viral response remained significant (p <0.0001).

Conclusions:  In this study, prolonged therapy was not associated with a higher sustained viral response rate compared to standard therapy. However, >50% of patients who achieved an undetectable HCV RNA level on therapy failed to complete their assigned treatment course, which precludes definitive hypothesis testing. These data suggest that longer pegINF + RBV therapy may not be feasible for many HIV-infected patients.