The authors concluded that the combined treatment peginterferon plus ribavirin was superior to other therapies in treatment of patients co-infected with different genotypes of HCV and with HIV. Despite some methodological limitations, the results are likely to be reliable.

To compare peginterferon with interferon in treatment of patients carrying different genotypes of hepatitis C virus (HCV) and co-infected with human immunodeficiency virus (HIV).

MEDLINE and EMBASE were searched from 1966 onwards. Search terms were reported. Reference lists of relevant publications were checked. Only English-language publications were included in the review.

Randomised controlled trials (RCTs) that compared peginterferon with interferon on sustained response rates in HCV/HIC-co-infected patients were eligible for inclusion. Eligible studies had to include participants with a detectable HCV ribonucleic acid (RNA) value and an infection duration of at least six months. Participants had to be treated for at least 24 weeks if infected with HCV genotypes 2 and 3, and for at least 48 weeks if infected with HCV genotypes 1 and 4. Eligible participants had to have a positive HIV antibody test and/or detectable HIV RNA values. The main outcome measure (sustained response rate) was defined as no detectable HCV six months after the cessation of treatment.

Drug doses and treatment regimens in the included studies were reported. Most studies included participants treated for 48 weeks with ribavirin and peginterferon and/or interferon. Mean age ranged from 37 to 45 across the studies. The proportion of males ranged from 63 to 86%. Mean body weight ranged from 62kg to 74.6kg. More than half of the participants had genotype 1. Where reported, 987 participants had genotype 1, 66 had genotype 2, 504 had genotype 3 and 160 had genotype 4.

Two reviewers independently selected the studies for inclusion.

Some aspects of quality were assessed. These included withdrawal rates, statistical methodology, confounding and blinding. Two reviewers independently assessed these quality criteria.

All analyses were conducted using the intention-to-treat populations.

Two reviewers independently extracted the studies. Any disagreements were resolved by discussion.

Meta-analyses that examined pooled relative risks (RRs) and 95% confidence intervals (CIs) were performed using the random-effects method. It appeared that heterogeneity was assessed using the Χ² test and I² statistic. Subgroup analyses were performed for type of peginterferon, drug regimen, dosage and genotype. A funnel plot was used to assess publication bias.

Six RCTs (n=1,756) were included in the review. Sample sizes ranged from 95 to 860 participants. The authors stated that the quality of included studies was high. Publication bias was detected for studies that evaluated the treatment of HCV genotypes 2 or 3, but not for genotypes 1 and 4.

Participants treated with peginterferon plus ribavirin had greater sustained response rates than participants treated with interferon plus ribavirin (RR 3.23, 95% CI 2.27 to 4.6; five trials). There was no statistical heterogeneity between studies.

Subgroup analyses demonstrated that both types of peginterferon (α-2a and α-2b) achieved higher sustained response rates compared with interferon. The combination of peginterferon plus ribavirin was more effective than peginterferon monotherapy. High-dose or low-dose ribavirin with peginterferon demonstrated significantly higher sustained response rates when compared to interferon. Peginterferon plus ribavirin remained superior to interferon by genotype, although efficacies varied.

There were no significant differences between the groups for adverse events.

The combined treatment peginterferon plus ribavirin was superior to other therapies in treatment of patients co-infected with different genotypes of HCV and with HIV.

The review addressed a clear question and was supported by appropriate inclusion criteria. Two databases were searched, but the authors did not appear to search for unpublished studies and this may have introduced publication bias. Only English-language publications were sought, which potentially introduced language bias. Steps were taken to minimise reviewer error and bias at all stages of the review process. The quality assessment criteria used did not appear robust (the authors did not appear to assess allocation concealment or method of randomisation) and the results of this assessment were not reported for each study. Thus, it was not possible to verify independently that these studies were of high quality. The studies appeared to be summarised appropriately in a meta-analysis. Despite some methodological limitations, the results are likely to be reliable.

Practice: The authors did not state any implication for practice.

Research: The authors stated that development of new antivirus drugs and antivirus strategies were urgently needed for reducing the lower sustained response rates of HCV genotypes 1 or 4 and HIV co-infected individuals.

National Natural Science Foundation of China, grant number 30470089.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.