1. Department of SOCIAL MEDICINE University of BRISTOL HEPATITIS C AND LIVER DISEASE PREVENTION Dr. Natasha Martin, DPhil Matthew Hickman, Daniela De Angelis, Peter Vickerman, Katy Turner, Vivian Hope, Norah Palmateer, Michael Sweeting, Sharon Hutchinson, Noel Craine, Graham Foster, David Goldberg, Alec Miners

2. Department of SOCIAL MEDICINE University of BRISTOL PUBLIC HEALTH IMPORTANCE  In UK  Liver disease is 5 th commonest cause of death  HCV/HBV 2 nd most important cause liver disease  Worldwide  HCV infection causes ~1/4 liver disease (over 350,000 deaths per year)

3. Department of SOCIAL MEDICINE University of BRISTOL ESTIMATED NUMBER OF PEOPLE INFECTED WITH ANTI-HCV ANTIBODIES Sweeting et al. Biostatistics 2008; De Angelis et al, Statistics in Meical Research 2009; Ross et al EJPH in press

4. Department of SOCIAL MEDICINE University of BRISTOL INTERVENTION EFFECTIVENESS  NSP is effective in reducing self-reported injecting risk behaviour  BUT on HCV transmission  Insufficient review level evidence that NSP is effective  Weak evidence that OST is effective  No review level evidence for other interventions Palmateer et al Addiction 2010 105: 844-59 (http://www.hepcscotland.co.uk/action-plan.html

5. Department of SOCIAL MEDICINE University of BRISTOL POOLING UK EVIDENCE ON INTERVENTION IMPACT Judd et al. BMJ 2005. Craine et al. J Epi & Inf 2009; Hope JVH 2010; Turner Addiction in press SiteYearDesignNHCV+veIncidence Sero- conversions Bristol2006RDS29959% 40 per 100py 14 Leeds2008RDS30260% 7.6 per 100py 2 Birmingham2009RDS31042% 5.2 per 100py 2 Glasgow2008-09 C'sectional NSP 94770% 10.0 per 100py 6 Wales2004-06Follow-up406/70026% 5.6 per 100 py 17 London2001-02Follow-up282/42843% 42 per 100py 49

6. Department of SOCIAL MEDICINE University of BRISTOL INTERVENTION EFFECT Intervention coverage New HCV infection Unadjust ed OR 95% CI Adjusted OR 95% CI (a) OST On OST*2.6%0.360.19 – 0.700.410.21 – 0.82 Not on OST6.9% (b) NSP ** ≥ 100% coverage3.8%0.520.28 -0.990.480.25 – 0.93 <100% coverage7.0% (c) COMBINED Full HR: OST and no injecting or ≥100% NSP 2.0%0.190.08 – 0.470.210.08 – 0.52 ≥100% NSP, No OST5.3%0.520.23 – 1.150.50.22 – 1.12 <100% NSP, On OST4.3%0.410.15 – 1.120.480.17 – 1.33 Minimal HR9.8% A djusted for the following covariates: female gender (AOR 2.1); homeless in last year (2,9); injected crack in last month (1.9); duration injecting <2.5 years (1.0) * Includes or ** Excludes 86 cases (involving 0 new HCV infections) who were on OST but reported no injections in the last month (cross-sectional studies) or last year (cohort studies).

7. Department of SOCIAL MEDICINE University of BRISTOL BUT WHAT ABOUT THE EFFECT ON HCV PREVALENCE?  HCV prevalence has decreased over time in some settings  But none have decreased HCV to low levels  Recent data from England/Wales suggests might be increasing ENGLAND AND WALES DATA Sweeting, M., et al., AJE 2009. 170: 352-60

8. Department of SOCIAL MEDICINE University of BRISTOL BRISTOL SURVEYS – 2006 : 2009  HCV Prevalence  ~53% 2006 (n=299)  ~57% 2009 (n=336)  Recent infections/incidence  ~40% 2006 (15 Antibody-ve PCR+ve)  <10% 2009 (3 Antibody-ve PCR+ve)  > 80% reduction in incidence

9. Department of SOCIAL MEDICINE University of BRISTOL CAN SCALING UP THE COVERAGE OF EXISTING INTERVENTIONS REDUCE HCV PREVALENCE?

10. Department of SOCIAL MEDICINE University of BRISTOL IMPACT OF CHANGING COVERAGE OF OST AND NSP FROM 50%: 0%, 60%, 70%, 80%

11. Department of SOCIAL MEDICINE University of BRISTOL IMPLICATIONS  NSP and OST can reduce HCV incidence.  And have averted infections  BUT unclear whether further scaling up feasible or could lead to substantial reductions in HCV prevalence  Other prevention options needed  Could HCV treatment have an impact?

12. Department of SOCIAL MEDICINE University of BRISTOL HCV ANTIVIRAL TREATMENT: BARRIERS AMONG ACTIVE IDUS  Antiviral treatment effective (~60%) for curing HCV infection and approved for active injecting drug users (IDUs)  BUT few currently being treated (<1%)  Perceived reluctance/concern over high rates of:  Non-completion/compliance  Re-infection following treatment

13. Department of SOCIAL MEDICINE University of BRISTOL MATHEMATICAL MODEL Non-responder infected IDUs HCV chronically infected IDUs Uninfected active IDUs Antiviral treatment Allow for reinfection Infection Death or cessation from each state New injectors Outcome: Impact on HCV prevalence Martin et al. J Hepatology 2011; J Theoretical Biology 2011

14. Department of SOCIAL MEDICINE University of BRISTOL PROJECTIONS

15. Department of SOCIAL MEDICINE University of BRISTOL RELATIVE PREVALENCE REDUCTIONS AT 10 YEARS WITH VARYING TREATMENT RATES ‘Baseline’: untreated endemic chronic infection prevalence Martin et al. J Hepatology 2011

16. Department of SOCIAL MEDICINE University of BRISTOL PREVALENCE REDUCTIONS AT 10 YEARS Population of 3500 IDUs, 1400 chronic infections 70 treated annually (20 per 1000 IDUs) 30% reduction by 2021 (40%  28%) 140 treated annually (40 per 1000 IDUs) 58% reduction by 2021 (40%  17%) Martin et al. J Hepatology 2011

17. Department of SOCIAL MEDICINE University of BRISTOL PROJECTIONS THROUGH TIME (5, 10, 20 YEARS) ANNUALLY TREATING 20 PER 1000 IDUS  Swift and substantial reductions at low prevalence  Significant reductions even at high prevalence  3500 IDUs, 1400 infected (40% prevalence), 70 treated/yr  15% reduction in 5 years (40  34%)  30% reduction in 10 years (40  28%)  Halved in 20 years (40  20%) Martin et al. J Hepatology 2011

18. Department of SOCIAL MEDICINE University of BRISTOL INCREMENTAL COST PER QALY VS. NO TREATMENT: EQUAL EFFICACY (SVR) FOR EX- AND ACTIVE IDU  Treating IDUs may be highly cost effective – and more cost effective (at prevalences <60%) than treating ex/nonIDU  Averts infections Martin et al in preparation

19. Department of SOCIAL MEDICINE University of BRISTOL IMPLICATIONS

20. Department of SOCIAL MEDICINE University of BRISTOL SCALE-UP – FROM MODELLING TO REALITY – EMPIRICAL DATA NEEDED  Trouble with models  Theoretical: projections not observations  Need to introduce heterogeneity: injecting risk/ HCV treatment uptake/ SVR  Model combined effects of HCV Rx, OST & NSP  BUT models can raise hypotheses/ provide theoretical framework/ justification for future work  Now empirical evidence required

21. Department of SOCIAL MEDICINE University of BRISTOL SCALING UP HCV TREATMENT  What are the best models/ways of delivering HCV treatment to injectors in community?  Start with OST population  Peer projects/ support  Treatment advocacy  Who is not worth starting treatment with i.e. compliance/SVR too low