1. Department of SOCIAL MEDICINE University of BRISTOL The primary prevention of hepatitis C among injectors: model projections of the impact of opiate substitution therapy, needle exchange and antiviral therapy Matt Hickman Natasha Martin, Peter Vickerman, Daniela De Angelis

2. Department of SOCIAL MEDICINE University of BRISTOL Primary Prevention of HCV  Epidemiology  Intervention Effectiveness  Modelling Impact of Prevention & HCV treatment  Case Finding - Implications

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

4. Department of SOCIAL MEDICINE University of BRISTOL UK: Majority of chronic HBV infection results from the migration of HBV carriers 2007: Estimated annual new chronic HBV infections in England and Wales UK HBV infections Estimates of chronic HBV infections Department of Health estimate Hepatitis B Foundation estimate Chronic HBV infection arising from acute HBV infection in resident population 269 per year Chronic HBV infection imported by people who acquired infection prior to migration 6,571 per year 0 50000 100000 150000 200000 250000 300000 350000 Hahné S et al. J Clin Virol 2004;29:211–20. Hepatitis B Foundation UK. Rising Curve: Chronic Hepatitis B Infection in the UK (2007)

5. Department of SOCIAL MEDICINE University of BRISTOL Estimated number of people infected with HCV: E&W 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)

6. Department of SOCIAL MEDICINE University of BRISTOL INTERVENTION EFFECTIVENESS: EMERGING EVIDENCE THAT OST AND NSP REDUCING HCV INCIDENCE DURING EXPOSURE Turner Addiction 2011 doi: 10.1111/j.1360-0443.2011.03515.x

7. Department of SOCIAL MEDICINE University of BRISTOL Pooling UK evidence on intervention impact Turner Addiction 2011 doi: 10.1111/j.1360-0443.2011.03515.x 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

8. Department of SOCIAL MEDICINE University of BRISTOL

9. 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). Turner Addiction 2011 doi: 10.1111/j.1360-0443.2011.03515.x

10. Department of SOCIAL MEDICINE University of BRISTOL But what about the effect on HCV prevalence?  20 million syringes distributed annually  5 fold increase in methadone prescription in last 10 years  BUT: little impact on HCV prevalence England and Wales data Sweeting, M., et al., AJE 2009. 170: 352-60

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

12. Department of SOCIAL MEDICINE University of BRISTOL Modeling transitions between OST and NSP & transmission of HCV Vickerman et al under review

13. Department of SOCIAL MEDICINE University of BRISTOL Impact of changing coverage of OST and NSP from 50%: 0%, 60%, 70%, 80%

14. Department of SOCIAL MEDICINE University of BRISTOL Implications  NSP and OST can reduce HCV incidence  Introducing OST & NSP will avert infections  OST is critical  BUT unclear whether alone NSP and OST could be lead to substantial reductions HCV prevalence  In UK sites already have high coverage sustained interventions & 40% chronic HCV prevalence in IDU  Other prevention options needed  Could HCV treatment have an impact?

15. Department of SOCIAL MEDICINE University of BRISTOL COULD SCALING UP HCV TREATMENT HAVE AN IMPACT ON HCV PREVENTION?

16. 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:  Non-completion/compliance  Re-infection following treatment

17. Department of SOCIAL MEDICINE University of BRISTOL Non-responder infected IDUs HCV-infected active IDUs Uninfected active IDUs Antiviral treatment Allow for reinfection Infection Outcome: Impact on HCV prevalence Martin et al. J Hepatology 2011; J Theoretical Biology 2011 New Injectors Cease/die DYNAMIC HCV TRANSMISSION MODEL

18. Department of SOCIAL MEDICINE University of BRISTOL Population of 3500 IDUs, 1400 chronic infections 70 treated annually (20 per 1000 IDUs) 30% reduction by 2022 (40%  28%) 140 treated annually (40 per 1000 IDUs) 58% reduction by 2022 (40%  17%) Martin et al. J Hepatology 2011 PREVENTION IMPACT RESULTS: PREVALENCE REDUCTIONS AT 10 YEARS

19. Department of SOCIAL MEDICINE University of BRISTOL Model 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

20. Department of SOCIAL MEDICINE University of BRISTOL BUT IS TREATING IDU FOR HCV COST EFFECTIVE?

21. Department of SOCIAL MEDICINE University of BRISTOL MODEL FORMULATION  Extend ‘infected’ state to include HCV disease progression stages  Attach health care costs and quality-adjusted life years (QALYs) to each state

22. Department of SOCIAL MEDICINE University of BRISTOL COST-EFFECTIVENESS RESULTS Mean incremental cost- effectiveness ratio, ICER (cost per QALY gained) IDUEx/non IDU 20% prevalence£521Dominated 40% prevalence£2,359Dominated 60% prevalenceDominated£6,803 Martin et al Hepatology 2012

23. Department of SOCIAL MEDICINE University of BRISTOL INCREMENTAL COST PER QALY GAINED: REDUCED TREATMENT SUCCESS RATES FOR IDU UK cost-effectiveness threshold Martin et al Hepatology 2012

24. Department of SOCIAL MEDICINE University of BRISTOL NICE ECONOMIC ANALYSIS: WAYS TO PROMOTE/OFFER TESTING OF HBV/HCV IN AT RISK POPULATIONS

25. Department of SOCIAL MEDICINE University of BRISTOL INTERVENTIONS TO PROMOTE HCV TESTING AMONG IDU Introducing HCV dried blood spot testing in prisons and specialist addiction services Pilot 1 UK cluster randomized controlled trial Increased testing rate by 2.63 and 3.61-fold in addiction services and prisons, respectively. General practitioner (GP) education and remuneration for targeted testing of former-IDU aged 30-54 years old Cullen et al. 2011 2 non-randomized controlled trial in Scotland Increased testing rate by 3.40-fold, also increased proportion positive HCV tests (yield) 1 Hickman et al. 2008 J Viral Hep 15(4):250-254 2 Cullen et al. 2011 J Pub Health (Ox) Epub

26. Department of SOCIAL MEDICINE University of BRISTOL INTERVENTIONS TO PROMOTE HCV/HBV TESTING AMONG UK MIGRANTS Less evidence for effective interventions in this group. Modelled hypothetical GP intervention Based on Lewis et al 2011 1 : Pakistani/British Pakistani people registered at GPs written and invited for an HCV/HBV test 1 Lewis H, et al. Gut, 2011. 60 (Suppl 2) a26.

27. Department of SOCIAL MEDICINE University of BRISTOL IMPLICATIONS

28. Department of SOCIAL MEDICINE University of BRISTOL NICE PDG  Consultation on recommendations – June  IF more people diagnosed AND undergo treatment then case finding likely to be cost-effective...

29. Department of SOCIAL MEDICINE University of BRISTOL Scale-up – from modelling to reality – empirical data needed  Trouble with models  Theoretical: projections not observations  Incorporate/test heterogeneity/ combine interventions… but empirical evidence required  NIHR PDG Grant “Can HCV treatment be delivered to injecting drug users in order to reduce HCV transmission and prevalence in the population: an empirical demonstration and evaluation”

30. Department of SOCIAL MEDICINE University of BRISTOL Scaling up HCV treatment and prevention  Audit current HCV treatment caseload  how far away from number required to observe impact in population  Pilot/develop HCV treatment in community  NIHR RfPB “Script in a day for injecting drug users: feasibility trial” RCT to evaluate accelerated access to opiate substitution therapy from BDP to establish whether increases uptake and retains patients in treatment