Determinants of hepatitis C virus treatment completion and efficacy in drug users assessed by meta-analysis

Abstract

Background: Hepatitis C virus (HCV)-infected drug users (DUs) have largely been excluded from HCV care. We conducted a systematic review and meta-analysis of the literature on treatment completion and sustained virologic response (SVR) rates in DUs. We assessed the effects of different treatment approaches and services to promote HCV care among DUs as well as demographic and viral characteristics.

Methods: Studies of at least 10 DUs treated with pegylated interferon/ribavirin that reported SVR were analyzed. Heterogeneity was assessed (Cochran test) and investigated (meta-regression), and pooled rates were estimated (random effects).

Results: Thirty-six studies comprising 2866 patients were retrieved. The treatment completion rate among DUs was 83.4% (95% confidence interval [CI], 77.1%-88.9%). Among studies that included addiction-treated and untreated patients during HCV therapy, the higher the proportion of addiction-treated patients, the higher the HCV treatment completion rate (P < .0001). After adjusting for human immunodeficiency virus (HIV)/HCV coinfection, sex, and treatment of addiction, support services during antiviral therapy increased treatment completion (P < .0001). The pooled SVR rate was 55.5% (95% CI, 50.6%-60.3%). Genotype 1/4 (P = .0012) and the proportion of HIV-coinfected DUs (P = .0173) influenced the SVR rate. After adjusting for HCV genotype 1/4 and HIV/HCV coinfection, the SVR rate was positively correlated with involvement of a multidisciplinary team (P < .0001).

Conclusions: Treatment of addiction during HCV therapy results in higher treatment completion. Our pooled SVR rate is similar to that obtained in registration trials in the general population. Treatment of addiction during HCV therapy will likely be important for HCV-infected DUs undergoing treatment with more complex regimens including direct-acting antivirals.

Figure 1.

A, Forest plot demonstrating the treatment completion rates and associated 95% confidence intervals for each of the studies included in the meta-analysis. Column labeled “Tx compl.” refers to the number of patients who completed treatment, and column labeled “% compl.” refers to the percentage of patients in each study who completed treatment. Treatment completion ranged between 36.4% and 100%. In 7 studies, all patients completed treatment including 5 studies that reported extremely high sustained virologic response rates [–21, 28, 41] and 2 that had small sample sizes [10, 32]. B, Funnel plot assessing publication bias for studies reporting treatment completion rates for hepatitis C virus infection. Treatment completion rates were transformed using the Freeman-Tukey double arcsine transformation [14] by the following formula: . Abbreviation: CI, confidence interval.

Figure 2.

A, Forest plot demonstrating the sustained virologic response (SVR) rate and associated 95% confidence interval for each of the studies included in the meta-analysis. Column labeled “SVR pts.” refers to the number of patients who achieved an SVR in the individual study. SVR was defined as absence of detectable peripheral hepatitis C virus RNA 24 weeks after treatment cessation. B, Funnel plot assessing publication bias for rate of sustained virologic response. Abbreviations: CI, confidence interval; SVR, sustained virologic response.

Figure 3.

Box plot illustrating sustained virologic response (SVR) rates by country of origin and includes all studies analyzed as part of meta-analysis as well as 4 outliers from Slovakia, Germany, Norway, and Serbia. The numbers in parentheses are the number of studies from each location. The SVR rate reported in US studies is significantly lower in comparison with other countries (P = .035). The box extends from the 25th to the 75th percentile. The line in the middle of the box is the median and the lines extending from either end of the box indicate the extent of the data beyond the 25th and 75th percentiles, and outliers, if any. Abbreviation: SVR, sustained virologic response.

Figure 4.

Forest plot demonstrating the early virologic response (EVR) rate and associated 95% confidence interval for each of the included studies that specified EVR rate. EVR was defined as undetectable hepatitis C virus (HCV) RNA or a 2 log₁₀ decrease in HCV RNA by week 12. Column labeled “EVR pts.” refers to the number of patients who achieved an EVR in the individual study. Abbreviations: CI, confidence interval; EVR, early virologic response.