Abstract: Fourteen trials were included. None of the included 2269 patients were previously treated for chronic hepatitis C. Peginterferon (either 2a, 180 microgram, or 2b, 1.5 microgram/kg, once weekly) plus ribavirin was more effective in achieving end of treatment and sustained virological response compared with interferon plus ribavirin (5 trials, 1340 patients) or peginterferon (2 trials, 714 patients). The benefit of peginterferon plus ribavirin was seen irrespective of HCV genotype although patients with genotype 1 or 4 had lower response rates (27%) than patients with genotype 2 or 3 (56%). The remaining trials compared different treatment regimens in patients who were treatment naive or had no virological response after three months of treatment, but overall they had not enough power to show any effect of increasing the dose of interferon or adding both amantadine or ribavirin. The overall mortality was 23/2111 patients with no significant differences between treatment regimens. Treatment increased the risk of adverse events including anaemia and flu-like symptoms, and several serious adverse events occurred including fatal lactic acidosis, liver failure, and suicide due to depression. Peginterferon plus ribavirin may be considered a treatment for patients with chronic hepatitis C and stable HIV who have not received treatment for hepatitis C as the intervention may clear the blood of HCV RNA. Supporting evidence comes mainly from the analysis of this non-validated surrogate outcome assessed in comparisons against other antiviral treatments. There is no evidence on treatment of patients who have relapsed or did not respond to previous therapy. Careful monitoring of adverse events is warranted.

Plain-language summary: Based on evidence from trials on HIV-negative patients with hepatitis C, the viral genotype, dose of treatment and duration of therapy may affect the treatment response. This review is the first to evaluate the antiviral effect of peginterferon, ribavirin or amantadine administered in different combinations for a patient group, which has not previously been treated for hepatitis C. A total of 14 randomised clinical trials with at total of 2269 patients have been included in this review.The present review suggests that peginterferon plus ribavirin may also be considered if patients have HIV. The dose of peginterferon was similar to that assessed in trials on patients without HIV (180 microgram or 1.5 microgram/kg once weekly), but the dose of ribavirin was somewhat lower in most trials (800 mg daily). There were considerable differences between the trials possibly related to the dose and duration of treatment or the proportion of patients with different hepatitis C virus genotypes. The benefit of treatment was seen when assessing the proportion of patients with a sustained loss of the hepatitis C virus from the blood and the proportion with improved liver biopsies. No significant differences were seen in clinical outcome measures, including mortality (1%, irrespective of treatment). There were several adverse events. Fatal lactic acidosis and liver failure occurred. Other adverse events included anaemia and flu-like symptoms that occurred more frequently among patients receiving peginterferon plus ribavirin. No significant differences were seen regarding the risk of depression, mortality, and progression to cirrhosis or to AIDS. Additional randomised trials are necessary to assess the effect in HIV and HCV co-infected patients of peginterferon plus ribavirin in relation to the duration of therapy, especially in patients with hepatitis C genotype 2 or 3. Additional trials comparing peginterferon plus ribavirin versus interferon plus ribavirin or peginterferon alone do not seem warranted.