nature publishing group 2335 © 2009 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY CLINICAL REVIEWS REVIEW INTRODUCTION Te prevalence of hepatitis C and human immunodefciency virus (HIV) coinfection ranges from ~10 to 50%, worldwide (1). Te prevalence of hepatitis C and HIV coinfection is espe- cially high among intravenous drug abusers and patients who have received contaminated blood or blood products (1,2). Afer the introduction of HAART (highly active antiretroviral therapy) in 1996, the prognosis of patients with HIV improved considerably (3). Since then, hepatitis C has become one of the main causes of death among patients with stable HIV (4,5). Clinical studies suggest that HIV worsens the course of chronic hepatitis C (4,6). Patients with HIV generally have high levels of hepatitis C virus RNA, and the progression to cirrhosis and end-stage liver disease is accelerated. Among patients with chronic hepatitis C, the proportion of those who clear the hepatitis C virus spontaneously is negli- gible both for patients without HIV and for those with HIV coinfection (1,7). Meta-analyses, including patients with- out HIV, found that several patients with chronic hepatitis C had no detectable hepatitis C virus RNA in their blood afer treatment with interferon plus ribavirin (8). Although several patients relapsed within the frst 6 months afer treatment, the proportion of patients with a 6-month sustained virological response was ~40%. In comparison, < 20% of patients with 10.1038/ajg.2009.311 Peginterferon Plus Ribavirin for Chronic Hepatitis C in Patients With Human Immunodeficiency Virus Lise Lotte Gluud, MD, DMSc 1,2 , Emanuela Marchesini, MD 3 and Alfonso Iorio, MD 3 OBJECTIVES: The aim of this study was to assess the effects of peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus (HIV). METHODS: Trials were identified through manual and electronic searches. Randomized trials comparing peginterferon plus ribavirin with other antiviral treatments for patients with chronic hepatitis C and HIV were included. The primary outcome measure was virological response at the end of treatment and after ≥ 6 months (sustained). Intention-to-treat meta-analyses including data on all patients who were randomized were carried out. RESULTS: Seven randomized trials were eligible for inclusion. The patients included had chronic hepatitis C and stable HIV and were not previously treated with interferon or ribavirin (treatment naive). The mean dosages were 180 or 1.5 μg/kg once weekly for peginterferon and 800 mg daily for ribavirin. The treatment duration ranged from 24 to 48 weeks. Peginterferon plus ribavirin increased the proportion of patients with an end-of-treatment or sustained virological response compared with interferon plus ribavirin or peginterferon alone. In subgroup analyses of trials comparing peginterferon plus ribavirin with interferon plus ribavirin, the proportion with a sustained virological response was 26% (109 of 423) for patients with genotype 1 or 4 and 57% (130 of 230) for genotype 2 or 3. Several adverse events occurred, including fatal lactic acidosis and liver failure, but there were no significant differences in mortality rates between treatment groups. CONCLUSIONS: Peginterferon plus ribavirin may be considered for treatment-naive patients with HIV and chronic hepatitis C. Adverse events should be monitored carefully. Am J Gastroenterol 2009; 104:2335–2341; doi:10.1038/ajg.2009.311; published online 9 June 2009 1 Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark; 2 Department of Internal Medicine, Gentofte University Hospital, Hellerup, Denmark; 3 Section of Internal and Vascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy. Correspondence: Lise Lotte Gluud, MD, DMSc, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Panum Institute, Copenhagen 2200, Denmark. E-mail: liselottegluud@yahoo.dk Received 15 September 2008; accepted 19 April 2009 CME