Background:  The need to treat hepatitis C has become a significant issue in HIV-infected subjects. We compared the safety, tolerability, and efficacy of a 48-week course of the standard (IFN--2b:  3 MIU x 3/week, n = 207) (INF group) to the pegylated (PEG-IFN--2b: 1.5 -m/kg x 1/w, n = 205) interferon (PEG group) both combined with ribavirin (800 mg/d, approximately 12 mg/kg/d).

Methods:  A randomized, multicenter, parallel-group, open-label trial. Inclusion criteria were:  HCV-RNA-positive and abnormal liver histology, CD4 >200, stable HIV RNA, stable HAART or off HAART. Primary endpoint was sustained virologic response (SVR):  loss of detectable serum HCV RNA at week 72 of follow-up.

Results: The 412 patients (40 years old, 74% male, 79% injection drug users [IDU]) were given HAART in 82%. Mean CD4 cell count was 514 + 229/mL, HIV RNA < 400 in 66% (mean HIV load in others: 3.7 + 0.7 logs). CDC class was A, B, and C in 53, 31, and 17%, respectively. HCV genotypes were 1 or 4 in 58%, 3 in 34%, and others in 8% (mean HCV load:  5.9 + 0.7 logs). The mean pre-treatment Metavir score was A 1.8 + 0.7, F 2.3 + 1.0, 39% of patients had F3-F4 of which 17% had sustained normal ALT. Baseline variables at entry were not different between groups. Treatment discontinuation occurred in 167 patients (42%) (86 IFN, 81 PEG) and severe adverse events in 127 (31%) (64 IFN, 63 PEG), including 6 symptomatic hyperlactatemia and 5 acute pancreatitis. A decrease was observed at week 12 of treatment, in INF and PEG groups respectively, significant for Hb (-1.4 g/dL vs -1.8, p = 0.002 ) and platelets (-19,000 vs -33,000, p = 0.04), not significant for neutrophils (-692 vs -1071), lymphocytes (-543 vs -662), or CD4 cells (-116 vs -124). SVR was achieved in 37 (18%) of IFN patients vs 54 (26%) of PEG patients, p = 0.031. In those who did not discontinue treatment, response rates were (weel 4:  12 % vs 20%; week 12:  34% vs 41%; week 24:  41% vs 54%; week 48:  34% vs 52%; week 72:  26% vs 35%). Virologic response at week 12 predicted SVR with 87% Positive Predictive Value and 87% Negative Predictive Value. SVR varied with genotypes 1 or 4 (11%) vs 3 or others (43%), but not with the Metavir score or the ribavirin dose adjusted for body weight. In responders, a significant decrease in Metavir scores F (-0.4 + 0.7) and A (-1.0 + 0.7) was observed.

Conclusions: In HIV/HCV co-infected patients, the combination of IFN--2b and ribavirin including the pegylated form of INF is associated with a superior HCV virologic response and a quite similar adverse-event profile.

Keywords: Randomized controlled trial; PEG-Interferon and ribavirin; Interferon and ribavirin