Background:  Sustained virological response rates to current treatments with pegylated interferon (peg-IFN) + ribavirin (RBV) are unsatisfying in patients co-infected with HIV.

Methods: Open-label pilot-study in which patients were randomized 1:1 to 48 wks of therapy with either the standard arm (peg-IFN-a2b 1.5 mg/kg/week + RBV 1000 to 1200 mg/day), or the induction arm (peg-IFN-a2b 3.0 mg/kg/week during the first 4 wks, 2.0 mg/kg/week during the next 4 wks, and 1.5 mg/kg/week during the remaining 40 weeks, + RBV in the same dose as the standard arm). Stratification factors included the hepatitis C virus (HCV) genotype (1 and 4 vs 2 and 3), CD4 cell count (< or >400/mm³) and plasma HCV RNA (< or >5.0 x 10e6 IU/mL). The primary efficacy end point was a sustained virological response (negative HCV RNA with TMA assay) 24 weeks after end of therapy. Safety was assessed. The analysis was conducted according to the intention-to-treat principle.

Results:  We randomized 26 patients of whom 24 started treatment. Final analysis is done in 23 patients (standard n = 10, induction n = 13) because 1 patient withdrew consent and refused us to use any of the collected data. This patient was considered a failure. Of 23 patients, 16 received HAART and the median CD4 count was 390/mm³ (range 150 to 1454); 10 patients had HCV genotype 3, 10 patients genotype 1 and 3 patients genotype 4. A sustained virological response was achieved in 8 of 23 patients (35%); 3 patients (30%) in the standard arm and 5 patients (38%) in the induction arm (p = 0.98). Only the decrease in serum HCV RNA during the first 4 weeks (OR 2.62 per log₁₀ IU decrease (95%CI 1.04 to 6.61) and genotype (OR for genotype 1 or 4, 0.12, 95%CI 0.02 to 0.87) were significant predictors of sustained virological response. Adverse events were typical of those previously reported for combination therapy. Serious adverse events that required hospitalization occurred in 5 of 23 patients (22%) (standard arm 3 vs 2 in the induction arm). One patient died of a pneumonia (possible TB), no other HIV-related complications occurred. No decompensation of the liver or clinical manifestation of mitochondrial toxicity (pancreatitis, lactic acidosis) was observed. However, during the first weeks of therapy dose reduction or treatment discontinuation of pegIFN because of neuropsychiatric side effects was necessary in almost one third of the patients in the induction arm versus none in the standard arm.

Conclusions:  Treatment with high dose pegIFN plus RBV did not improve sustained virological response compared with standard combination therapy. High dose pegIFN caused more neuropsychiatric toxicity, making it an unattractive treatment option.