Injection drug users (IDUs) constitute 60% of the approximately 5 million people in the United States infected with hepatitis C virus (HCV), and the majority of drug users in opioid agonist treatment programs have HCV. Even though there are effective HCV treatments, alarmingly few drug users and opioid agonist maintained patients have initiated HCV treatment. Because HCV has a discrete course of treatment lasting only 24 to 48 weeks and its backbone is once-weekly subcutaneous pegylated interferon injections, it may be ideally suited for directly observed treatment (DOT) management. To test this, we have designed a small randomized controlled trial of modified DOT (mDOT) for HCV treatment (both pegylated interferon and ribavirin) in drug users enrolled in opioid agonist treatment. The goal of this mentored award is to enhance the clinical research skills of Alain Litwin, M.D., M.P.H., M.S., through research on integrating HCV treatment with substance abuse treatment. Dr. Litwin's training plan involves formal mentorship in the following areas: implementing comprehensive DOT programs in opiate agonist programs, measuring and analyzing adherence in drug users, designing behavioral interventions for drug users, clinical trial study design, advanced statistical methods, and community-based participatory research.
The specific aims of this proposal are: (1) To determine in randomized trial whether modified directly observed HCV treatment (pegylated interferon alfa-2a plus ribavirin) provided on-site at a methadone program is more efficacious than self-administered HCV treatment for enhancing adherence;(2) To determine the impact of providing on-site HCV treatment on virologic outcomes, and to determine the association between HCV treatment adherence and virologic outcomes. As a sub-aim, we will also determine whether mDOT is more efficacious than self-administered HCV treatment for achieving HCV treatment outcomes;and (3) To identify individual-level factors (e.g. active drug and alcohol use, active psychiatric illness, housing status, social support, beliefs and knowledge about HCV medications, motivation to adhere, self-efficacy, and medication side effects) influencing HCV treatment adherence and HCV treatment outcomes. Findings from this project will be used to inform the development of a large randomized trial of the efficacy and cost-effectiveness of modified directly observed HCV care versus regular on-site care.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Human Development Research Subcommittee (NIDA)
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Khalsa, Jagjitsingh H
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Albert Einstein College of Medicine
Internal Medicine/Medicine
Schools of Medicine
United States
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Batchelder, A W; Brisbane, M; Litwin, A H et al. (2013) "Damaging what wasn't damaged already": Psychological tension and antiretroviral adherence among HIV-infected methadone-maintained drug users. AIDS Care :
Nahvi, Shadi; Litwin, Alain H; Heo, Moonseong et al. (2012) Directly observed antiretroviral therapy eliminates adverse effects of active drug use on adherence. Drug Alcohol Depend 120:174-80
Litwin, Alain H; Smith, Bryce D; Drainoni, Mari-Lynn et al. (2012) Primary care-based interventions are associated with increases in hepatitis C virus testing for patients at risk. Dig Liver Dis 44:497-503
Litwin, Alain H; Berg, Karina M; Li, Xuan et al. (2011) Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics. BMC Infect Dis 11:315
Cunningham, Chinazo O; Sohler, Nancy L; Cooperman, Nina A et al. (2011) Strategies to improve access to and utilization of health care services and adherence to antiretroviral therapy among HIV-infected drug users. Subst Use Misuse 46:218-32
Harris Jr, Kenneth A; Arnsten, Julia H; Litwin, Alain H (2010) Successful integration of hepatitis C evaluation and treatment services with methadone maintenance. J Addict Med 4:20-6
Litwin, Alain H; Harris Jr, Kenneth A; Nahvi, Shadi et al. (2009) Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program. J Subst Abuse Treat 37:32-40