1. Hepatitis C prevention among people who inject drugs: reducing transmission in PWID by scaling up HCV treatment, OST and needle exchange services Matt Hickman, Natasha Martin, Peter Vickerman

2. Acknowledgements NIHR Health Protection Research Unit in Evaluation of Interventions Health Protection Scotland: HCV Action Plan NIHR PDG Can HCV treatment be delivered to injecting drug users… European Commission Drug Prevention and Information Programme (DIPP) “Treatment as Prevention in Europe…” NIHR (HS&DR) (12/3070/13) - Assessing the impact and cost- effectiveness of NSP on HCV The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Collaborators:- Sharon J Hutchinson, Graham R Foster, John F Dillon, Fiona Gordon, Javier Vilar, Matthew Cramp, Stephen Ryder, David J Goldberg, Daniela De Angelis, Will Irving, Viv Hope, Noel Craine, Marion Lyons, Norah Palmateer, Esther Aspinall

3. EPIDEMIOLOGY

4. > 90% HCV acquired in UK among PWID Sweeting et al. Biostatistics 2008; De Angelis et al, Statistics in Med Research 2009; Ross et al EJPH 2011 ~15,000 White; 11,000 (IPB)

5. OST/HIGH COVERAGE NSP (HC_NSP) EFFECTIVENESS Use recent pooled UK evidence for impact of harm reduction on an individual’s risk of recent HCV infection 1 Effect EstimatesAOR 1 95% CI HC_NSP0.480.30.9 OST0.410.20.8 OST and HC_NSP0.210.10.5 1 adjusted for: gender, crack, homeless, injecting duration HC_NSP is defined as exchanging more syringes than you inject Turner K et al. Addiction 2011; 106:1978-88

6. CAN SCALING UP COVERAGE OF OST & NSP ACHIEVE FURTHER SUBSTANTIAL REDUCTIONS IN HCV AMONG PWID

7. Modeling transitions between OST and NSP & transmission of HCV Vickerman et al Addiction 2012 doi:10.1111/j.1360-0443.2012.03932.x

8. Impact of changing coverage of OST and NSP from 50%: 0%, 60%-80% Vickerman et al Addiction 2012 doi:10.1111/j.1360-0443.2012.03932.x

9. SCALING UP HCV TREATMENT AS PREVENTION

10. Non-SVR infected PWID Chronically infected PWID Uninfected PWID Antiviral treatment Allow for re-infection New PWID Cease/die Acutely infected PWID Infection Spontaneous clearance Need Dynamic Model to Assess Intervention Impact on HCV Prevalence Martin NK, Vickerman P, Foster GR, Hutchinson SJ, Goldberg DJ, and Hickman M. J Hep 2011; 54:1137-44

11. MODELLING HCV TREATMENT AS PREVENTION HCV RELATIVE PREVALENCE REDUCTIONS AT 10 YEARS WITH PEGIFN+RBV

12. Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, and Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modelling the impact of antiviral treatment, needle and syringe programmes, and opiate substitution therapy. Clinical Infectious Diseases 2013 40% chronic prevalence Dark red: modest (<20%) impact, high HCV Orange: ~50% impact White: >80% impact COMBINATION PREVENTION SCALE-UP (OST/NSP/DAAS): 10 YEAR RELATIVE PREVALENCE REDUCTIONS WITH NO BASELINE COVERAGE OF OST/NSP AND USING DAAs >40% reduction requires HCV treatment OST&NSP increases benefit of HCV treatment

13. HCV TREATMENT & TREATING PWID IS COST-EFFECTIVE SO IN NEW DAA ERA - WHICH PATIENTS SHOULD BE TARGETED?

15. Cost-effectiveness efficiency frontiers – 20% chronic HCV new DAA Treating PWID/non-exPWID with mild or moderate HCV compared to delayed treatment until cirrhosis. Treatment scenarios above frontier are dominated (more expensive, fewer benefits)

16. Cost-effectiveness efficiency frontiers – 40% chronic HCV new DAA

17. Cost-effectiveness efficiency frontiers – 60% chronic HCV new DAA

18. ARE CURRENT HCV TREATMENT RATES SUFFICIENT?

19. Blue: Baseline in 2014 White box: 2024, No scale-up, ITT SVR with IFN/RBV Bristol E London Manchester Nottingham Plymouth Dundee N Wales HCV chronic prevalence among PWID (%) TREATMENT IMPACT IN SEVEN UK CITIES WITH CURRENT RATES/SVR Martin NK, JVH 2014

20. Blue: Baseline in 2014 White box: 2024, No scale-up, ITT SVR with IFN/RBV Black: 2024, Scale-up to 26/1000 annually with IFN-free DAAs (all genotypes) in 2016 Bristol E London Manchester Nottingham Plymouth Dundee N Wales HCV chronic prevalence among PWID (%) TREATMENT IMPACT IN SEVEN UK CITIES WITH SCALE-UP/DAAs Martin NK, JVH 2014

21. HCV ELIMINATION – MYTH OR REALITY

22. Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, and Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modelling the impact of antiviral treatment, needle and syringe programmes, and opiate substitution therapy. Clinical Infectious Diseases 2013 COMBINATION PREVENTION SCALE-UP (from 50% OST/NSP & DAAS): 10 YEAR RELATIVE PREVALENCE REDUCTIONS 40% CHRONIC HCV Towards Elimination: scaling up HCV treatment rates to 30-40 per 1000PWID & 60% OST&NSP coverage reduces HCV prevalence by 60-80% in 10 years.

23. HCV prevalence reduction – combining interventions HCV treatment scale-up essential to achieve substantial reductions in HCV prevalence Current treatment rates maybe insufficient to achieve observable reductions (in UK) OST&NSP increase benefits of HCV treatment as prevention HCV treatment of PWID is cost-effective – and in many scenarios more cost-effective than treating ex/non-PWID or delaying treatment until cirrhosis. Now need empirical evidence to test model projections