Hepatitis C virus (HCV)-related deaths now exceed HIV-related deaths in the US. Throughout the world, HCV is hyperendemic in people who inject drugs (PWID). New outbreaks of acute HCV infection are unfolding in HIV-positive men who have sex with men (MSM) and in 15-24 year olds who have transitioned from abuse of prescription opioids to illicit opiate injection. In patients with chronic HCV infection, 20-25% wil develop liver disease which may manifest as cirrhosis, liver failure or hepatocellular carcinoma (HCC). The prognosis for HCC is extremely poor, and HCV is the chief etiologic agent for this type of cancer. Recent discoveries in HCV prevention and treatment provide a great opportunity to reverse the trend toward increasing rates of HCV, HCV/HIV co-infection, and HCC. This study will use the methods of Implementation Science - research synthesis, mathematical modeling and simulation, and comparative effectiveness analyses - to determine how best to constitute a portfolio of interventions for the prevention and control of HCV and its consequences while taking into limited resources and underlying epidemiologic and social network features account. A dissemination plan will make extensive use of technology, including social media, and guidance from key stakeholders. These are our specific aims: 1. Synthesize evidence characterizing a) transition from misuse of prescription opioids to drug injection, b) HCV epidemiology and prevention for PWID and HIV+ MSM, and c) progression and treatment of HCV disease in these two groups, to derive best estimates to populate our HCV natural history and transmission models. 2. Use agent-based modeling to estimate the effects of scale-up of individual and combined prevention- and treatment-related interventions on HCV transmission and natural history in PWID and HIV+MSM. 3. Determine the combination of interventions for particular budget and epidemiologic scenarios that a) minimizes acute and chronic HCV infections, including HIV/HCV co-infection, b) prevents the greatest number of cases of HCV-related HCC and other serious sequelae, c) maximizes life expectancy and quality- adjusted life expectancy and d) reduces health disparities. 4. In collaboration with our Dissemination Advisory Board, apply an integrated knowledge-exchange approach to providing our target audiences (policymakers, public health and harm reduction practice communities, PWID and HIV+MSM) with the knowledge and tools to implement evidence-based HCV control strategies or reduce personal risk of infection and its consequences. The broad objective of this study is to provide an evidence base to guide allocation of scarce public resources in the US and other countries where HCV is principally transmitted among PWID. This will be accomplished by synthesizing, modeling and translating very recent developments in HCV epidemiology, prevention and treatment into practical tools to optimize population health.

Public Health Relevance

Statement The goal of this study is to help decision makers improve population health by providing guidance on the most effective set of interventions to control hepatitis C virus (HCV) infection in people who inject drugs and HIV- positive men who have sex with men. In the US, HCV is the main causal factor in hepatocellular carcinoma which has a very poor prognosis, and HCV-related deaths now exceed deaths related to HIV. This research will synthesize evidence as to the effectiveness of different intervention strategies in terms of both individual benefit (preventing HCV infections in these populations, reducing HCC and other consequences of HCV), and in terms of societal benefit (reducing health care costs and impact on life expectancy).

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Dissemination and Implementation Research in Health Study Section (DIRH)
Program Officer
Lambert, Elizabeth
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New York University
Schools of Nursing
New York
United States
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Platt, Lucy; Reed, Jennifer; Minozzi, Silvia et al. (2016) Effectiveness of needle/syringe programmes and opiate substitution therapy in preventing HCV transmission among people who inject drugs. Cochrane Database Syst Rev 2016:
Jordan, Ashly E; Perlman, David C; Neurer, Joshua et al. (2016) Prevalence of hepatitis C virus infection among HIV+ men who have sex with men: a systematic review and meta-analysis. Int J STD AIDS :
Reed, Jennifer R; Jordan, Ashly E; Perlman, David C et al. (2016) The HCV care continuum among people who use drugs: protocol for a systematic review and meta-analysis. Syst Rev 5:110
Dombrowski, Kirk; Khan, Bilal; Habecker, Patrick et al. (2016) The Interaction of Risk Network Structures and Virus Natural History in the Non-spreading of HIV Among People Who Inject Drugs in the Early Stages of the Epidemic. AIDS Behav :
Smith, Daniel J; Jordan, Ashly E; Frank, Mayu et al. (2016) Spontaneous viral clearance of hepatitis C virus (HCV) infection among people who inject drugs (PWID) and HIV-positive men who have sex with men (HIV+ MSM): a systematic review and meta-analysis. BMC Infect Dis 16:471
Smith, Daniel J; Combellick, Joan; Jordan, Ashly E et al. (2015) Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis. Int J Drug Policy 26:911-21
Khan, Bilal; Dombrowski, Kirk; Curtis, Ric et al. (2015) Estimating Vertex Measures in Social Networks by Sampling Completions of RDS Trees. Soc Netw 4:1-16
Hagan, Holly; Jordan, Ashly E; Neurer, Joshua et al. (2015) Incidence of sexually transmitted hepatitis C virus infection in HIV-positive men who have sex with men. AIDS 29:2335-45
Hagan, Holly; Neurer, Joshua; Jordan, Ashly E et al. (2014) Hepatitis C virus infection among HIV-positive men who have sex with men: protocol for a systematic review and meta-analysis. Syst Rev 3:31
Jordan, Ashly E; Jarlais, Don Des; Hagan, Holly (2014) Prescription opioid misuse and its relation to injection drug use and hepatitis C virus infection: protocol for a systematic review and meta-analysis. Syst Rev 3:95

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