Effectiveness and Tolerability of Combination Treatment of Chronic Hepatitis C in Illicit Drug Users: Meta-Analysis of Prospective Studies

Background: Hepatitis C virus (HCV) infection is a global health problem. In Western countries, illicit drug users (IDUs) constitute the largest proportion of HCV patients. International guidelines no longer regard ongoing illicit drug use as a contraindication to antiviral therapy for chronic hepatitis C (CHC). Nonetheless, in clinical practice, few IDUs have access to HCV treatment, likely because many physicians believe these patients will have poor adherence or a lack of treatment efficacy. Objective: The aim of this study was to assess effectiveness and tolerability of combination treatment with ribavirin plus recombinant or pegylated interferon-a in the treatment of CHC in IDUs. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched for relevant studies published in English between 2000 and December 2008. The following terms were searched: chronic hepatitis C, interferons, antiviral agents, methadone, and substance-related disorders. Full-text articles and abstracts were searched using predefined criteria. A manual search of abstracts from 8 international meetings of hepatologists was also conducted. Only prospective studies with a sample size >15 and a homogeneous treatment schedule were included. Articles were extracted independently by 2 of the authors using an electronic standardized form including study quality indicators. Results: Sixteen prospective studies were included, and data from a cohort of 953 IDUs were analyzed. The estimated overall sustained virologic response (SVR) and dropout (DO) rates in IDUs were 52% (95% CI, 44%-60%) and 26% (18%-35%, 95% CI), respectively. The rate of psychiatric severe adverse events (SAEs) that led to treatment discontinuation was 2% (95% CI, 1%-3%). These prevalences were not significantly different from those reported in registration trials of treatment of CHC that excluded IDUs from the study population (SVR, 50% [95% CI, 39%-61%]; DO, 26% [95% CI, 12%-41%]; and psychiatric SAEs, 2% [95% CI, 0%-6%]). By subgroup analysis, active ongoing drug use negatively affected the rate of treatment success (39% [95% CI, 30%-49%] vs 55% [95% CI, 45%-64%]; P = 0.02). Conclusion: Based on data from 16 prospective clinical studies of CHC treatment in IDUs published in the past 10 years, findings on effectiveness and tolerability are comparable to those in the general population. (Clin Ther. 2010;32:2139-2159) (C) 2010 Elsevier HS Journals, Inc.