November 11, 2013

Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals

Hepatology

Volume 58, Issue 5, pages 1598–1609, November 2013

Viral Hepatitis

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Natasha K. Martin1,2,*, Peter Vickerman2,  Jason Grebely3, Margaret Hellard4,  Sharon J. Hutchinson5,6, Viviane D. Lima7,  Graham R. Foster8, John F. Dillon9, David J. Goldberg5, Gregory J. Dore3, Matthew Hickman1

Article first published online: 26 AUG 2013

DOI: 10.1002/hep.26431

© 2013 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The views expressed in this article are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health.

This work was produced under the terms of the postdoctoral research training fellowship (to N. K. M.) issued by the National Institute for Health Research (NIHR). P. V. was supported by Medical Research Council New Investigator Award G0801627. J. G. was supported by a National Health and Medical Research Council (NHMRC) Career Development Fellowship. M. Hellard was supported by an NHMRC Project Grant and the Victorian Operational Infrastructure Support Program. V. D. L. was supported by a National Institute on Drug Abuse Michael Smith Foundation for Health Research Scholar Award. G. J. D. was supported by a NHMRC Practitioner Research Fellowship. The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, University of New South Wales. M. Hickman was supported by the NIHR School of Public Health Nationally Integrated Quantitative Understanding of Addiction Harm MRC addiction research cluster and The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement, a UK Clinical Research Collaboration (UKCRC) Public Health Research Centre of Excellence. Funding was also received from the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council (grant RES-590-28-0005), the Medical Research Council, the Welsh Assembly Government, and the Wellcome Trust (grant WT087640MA) under the auspices of the UKCRC.

Potential conflict of interest: N. K. M. has received an honorarium for speaking at a conference sponsored by Janssen. J. G. owns stock in Gilead and is a member of an advisory board for Merck. S. J. H. has received honoraria for speaking at conferences sponsored by MSD and Janssen and consults for Janssen. G. R. F. has received funding from Roche, Novartis, Janssen, Gilead, Bristol-Meyers Squibb, Boehringer Ingelheim, Idenix, Abbott, and Merck for consultancy and lectures. D. J. G. is a member of advisory boards and undertakes consultancy for Merck and Janssen. G. J. D. is a consultant/advisor and has received research grants from Roche, Merck, Janssen, Gilead, Bristol-Myers Squibb, and Abbott.

See Editorial on Page 1523

Abstract

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon-free direct-acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three-quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale-up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2-, 13-, and 15-fold increases, respectively). Scale-up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three-quarters within 15 years. Less impact occurs with delayed scale-up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US $3.2 million in Edinburgh and approximately $50 million in Melbourne and Vancouver. Conclusion: Interferon-free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale-up, and should be addressed. (Hepatology 2013;58:1598–1609)

The global burden of hepatitis C virus (HCV) infection continues to rise.[1, 2] The core of the HCV epidemic in the developed world occurs among people who inject drugs (PWID), who comprise the majority of new (80%) and existing (60%) cases.[1] Globally, HCV seroprevalence (>60% in most countries)[3] and incidence (5%-40% annually)[4, 5] remains high among PWID. Prevention strategies, such as needle and syringe programs (NSP) and opiate substitution therapy (OST), can reduce HCV transmission and have maintained low levels of human immunodeficiency virus (HIV) infection in many settings, but they are insufficient to achieve substantial reductions in HCV prevalence.[6-9] This is partly because high HCV prevalence and long injecting duration among PWID in many settings combine such that the intervention coverage required for major prevalence reductions is unobtainable and unsustainable.[9] Given that there is no HCV vaccine, alternative strategies for HCV prevention are urgently needed.

In HIV, the demonstration that antiretroviral therapy given to HIV-infected individuals can prevent secondary transmission has generated considerable excitement[10] and suggests that we may have reached a tipping point for preventing HIV transmission.[11] In contrast to HIV, HCV is curable and therapy is finite. Therefore, HCV treatment as prevention may provide even greater opportunity for preventing onward HCV transmission and directly reducing HCV chronic prevalence.

Mathematical modeling studies have suggested HCV treatment for PWID could be an effective[12-16] and cost-effective[17] intervention to prevent HCV transmission. However, these studies only considered treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV). The feasibility of expanding this treatment regimen as a strategy for treatment as prevention is limited, given the poor tolerability and limited uptake of PEG-IFN+RBV therapy, particularly among PWID.[18, 19] However, therapeutic options for HCV are evolving rapidly. Preliminary data from IFN-free direct-acting antiviral (DAA) therapy phase 2 trials indicates that in the near future, regimens will be available with markedly reduced toxicity, high efficacy (>90% cure), improved dosing schedules (once or twice-daily), and shortened treatment duration (6-24 weeks).[20-22] Such advances indicate that a HCV treatment as prevention strategy among PWID may be feasible in the very near future.

We project the potential impact of DAA therapy on HCV prevalence in three international settings with varied prevalence.

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