Abstract
BackgroundMost methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users.Methods/DesignWe plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV-infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm.DiscussionThis paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence.Trial RegistrationClinicalTrials.gov: NCT01442311
Highlights
Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment
This paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual
Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future directly observed therapy (DOT) programs, and can guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence
Summary
This study represents the first randomized controlled trial of a directly observed HCV program in a methadone program that focused on the contribution of directly observed ribavirin. A recent randomized trial of HCV treatment in methadone-maintained patients focused on directly observed pegylated interferon, and compared weekly provider-administered (DOT) pegylated interferon alfa2a in combination with self-administered ribavirin to self-administered pegylated interferon alfa-2a in combination with self-administered ribavirin. Subjects in both arms took ribavirin on their own, more subjects in the DOT pegylated interferon group were >97% adherent with planned cumulative doses of both peginterferon alfa-2a and ribavirin, as well as with the prescribed duration of treatment [10]. Some aspects of our study design may improve adherence in the TAU arm, and reduce our measured effect size These include weekly provider-administered pegylated interferon, frequent visits with research assistants, and participation with HCV support groups. With newer regimens for HCV treatment emerging (e.g. telaprevir and boceprevir) that involve multiple oral agents in combination with pegylated interferon along with the potential for inducing resistance, DOT strategies may have even greater clinical benefit [31,32]
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