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Matt Hickman, Natasha Martin, Peter Vickerman, Hannah Fraser, Zoe Ward

Model and empirical evidence on the effectiveness of interventions to prevent HCV among people who inject drugs. Matt Hickman, Natasha Martin, Peter Vickerman, Hannah Fraser, Zoe Ward. Acknowledgements & Disclosure/ CoI. NIHR Health Protection Research Unit in Evaluation of Interventions

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Matt Hickman, Natasha Martin, Peter Vickerman, Hannah Fraser, Zoe Ward

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  1. Model and empirical evidence on the effectiveness of interventions toprevent HCV among people who inject drugs Matt Hickman, Natasha Martin, Peter Vickerman, Hannah Fraser, Zoe Ward

  2. Acknowledgements & Disclosure/CoI • NIHR Health Protection Research Unit in Evaluation of Interventions • Health Protection Scotland: HCV Action Plan • European Commission Drug Prevention and Information Programme (DIPP) “Treatment as Prevention in Europe: Model Projections [JUST/2013/DPIP/AG/4812] • NIHR (HS&DR) (12/3070/13) - Assessing the impact and cost-effectiveness of NSP • MH received honoraria from Abbvie, MSD, Janssen, Gilead. 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 Hutchinson, Vivian Hope, Graham Foster, John Dillon, Sema Mandell, Mary Ramsay, Helen Harris, Ross Harris, Fiona Gordon, Javier Vilar, Matthew Cramp, Stephen Ryder, David Goldberg, Daniela De Angelis, Will Irving, Noel Craine, Marion Lyons, Norah Palmateer, Esther Aspinall, Lucy Platt, Amy Master, Maria Prins, Bernd Schulte, Henrikki Bummer, Viktor Mravcik, Martin Kåberg, Anne Ovrehus, Geert Robaeys, PatriziaVarreiri, Marie Jauffret, Olav Dalgard, MajcaMatičič, Hannah Fraser, Zoe Ward, Jason Grebely, Greg Dore, Margaret Hellard, Bristol Drug Project. Silvia Minozzi, Holly Hagan, Clare French, LouisaDegenhardt, Lisa Maher

  3. http://www.emcdda.europa.eu/publications/insights/hepatitis-c-among-drug-users-in-europehttp://www.emcdda.europa.eu/publications/insights/hepatitis-c-among-drug-users-in-europe

  4. effectiveness of needle/syringe programmes and opiate substitution therapy in preventing HCV transmission among people who inject drugs

  5. Impact of current OST exposure (adjusted estimates) • 12 studies: • 6361 participants • 1030 HCV cases • 50% reduction in risk of HCV • Little heterogeneity • GRADE: Low Evidence.

  6. Impact of high NSP by region (unadjusted analyses) • 7 studies • High heterogeneity (I2=79%) • Weak evidence overall – RR 0.77 • In Europe NSP associated with 66% reduction in HCV • Grade: very low evidence

  7. Impact of NSP and OST • High NSP with OST • 4 studies • 3356 participants • 518 HCV cases Reduced HCV by 71% • moderate heterogeneity • Low NSP with OST • 3 studies • 3071 participants • 449 HCV cases, • Reduced HCV by 24% • GRADE: low evidence

  8. Can scaling up coverage of OST & NSP achieve further substantial reductions in HCV among PWID

  9. Why HCV treatment is needed for prevention • Opioid substation therapy (OST) and needle and syringe programmes (NSP) can reduce HCV prevalence, but unclear whether can lead to substantial reductions Vickerman et al. Addiction 2012.

  10. COMBINATION PREVENTION SCALE-UP: 10 YEAR RELATIVE PREVALENCE REDUCTIONS WITH NO BASELINE COVERAGE OF OST/NSP AND USING DAAs 40% chronic prevalence • Dark red: modest (<20%) impact, high HCV • Orange: ~50% impact • White: >80% impact • >40% reduction requires HCV treatment • OST&NSP increases benefit of HCV treatment Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, and Vickerman P. C. Clinical Infectious Diseases 2013

  11. DAA TREATMENT RATES TO HALVE CHRONIC PREVALENCE IN 10 YRS WITH HARM REDUCTION Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, and Vickerman P. C. Clinical Infectious Diseases 2013

  12. Changing clinical guidelines & Treatment prioritisation

  13. RECOMMENDATIONS ON TREATMENT OF HEPATITIS C 2015 A1: “Further research is very unlikely to change confidence in the estimate of the effect. B1: “Further research is likely to have an impact on our confidence in the estimate of effect”

  14. ECONOMIC MODELING SUPPORTS TREATMENT FOR PWID AND PRIORITIZATION OF PWID FOR EARLY TREATMENT • Are DAAs cost-effective for PWID? • YES - in UK, Australia, Netherlands • Early DAA treatment for PWID cost-effective compared to delay to cirrhosis1 • Who do we prioritize after cirrhotics? • Traditional thinking is most cost-effective to prioritize by disease stage • BUT if include prevention benefits, more cost-effective to prioritize early treatment to PWID regardless of liver disease stage, then to former PWID with moderate disease in 20%/40% chronic prevalence settings1 Early treatment vs delay to cirrhosis UK willingness-to-pay threshold £1 = 1€ = $1.30 1. Martin NK et al. J Hepatol 2016 2. Scott N et al. J Gastro Hep 2016 3. Van santen DK PLoS ONE 2016

  15. MORE COST-EFFECTIVE TO PRIORITIZE EARLY TREATMENT FOR PWID INSTEAD OF BY STAGE IN 20/40% PREV SETTINGS 20% chronic prev among PWID 40% chronic prev among PWID 60% chronic prev among PWID *£20,000 willingness to pay. Martin NK et al. J Hepatol 2016: 65(1):17-25. Economic modeling supports treatment for and prioritization of PWID – essential for achieving elimination targets

  16. NUMBER OF NEW INFECTIONS AVERTED PER EARLY TREATMENT 20% chronic prev among PWID 40% chronic prev among PWID 60% chronic prev among PWID Martin NK et al. J Hepatology 2016

  17. Are current hcv treatment rates sufficient to achieve a measurable change in hcv transmission in Europe?

  18. Results 1: % of estimated PWID with chronic infections treated at baseline (2015/16) Fraser et al, (2017) Journal of Hepatology, In press

  19. Results 2: Baseline chronic prevalence Fraser et al, (2017) Journal of Hepatology, In press

  20. Results 2: 10 year impact on chronic prevalence if swop to DAAs $ z-score < 0.5 (unlikely to observe a difference 2016-2026) + z-score 0.5-1.5 (may be able to observe a difference 2016-2026) * z-score 1.5-3 (increasingly likely to be able to observe a difference 2016-2026) # z-score >3 (highly likely to be able to observe a difference 2016-2026) Fraser et al, (2017) Journal of Hepatology, In press

  21. Results 4: Treatment needed per 1000 PWID to reduce HCV to 2 per 100pyrs by 2026 Purple: Number of treatments per 1000 PWID at baseline (2015/16) Green: Number of treatments needed per 1000 PWID in 2016/17 with current OST and NSP. Yellow: Number of treatments needed per 1000 PWID in 2016/17 with 80% coverage OST and NSP. Fraser et al, (2017) Journal of Hepatology, In press

  22. Results 4: Treatment needed per 1000 PWID to reduce HCV to 2 per 100pyrs by 2026 Purple: Number of treatments per 1000 PWID at baseline (2015/16) Green: Number of treatments needed per 1000 PWID in 2016/17 with current OST and NSP. Yellow: Number of treatments needed per 1000 PWID in 2016/17 with 80% coverage OST and NSP. Fraser et al, (2017) Journal of Hepatology, In press

  23. More examples – cost-effectiveness & combining interventions

  24. HCV in Scott County, Indiana Treatment scale-up to reduce HCV to low levels Projected number of PWID needing HCV treatment annually Percentage of infections treated in mid-2016 to mid-2017 • 90% reduction by 2025 only always possible if MAT+SSP also scaled up. • 111-121 treatments per 1000 PWID treated annually (18.2-19.9%) to decrease prev/inc. • Again treatments doubled without HR if still possible. • Not possible to decrease prevalence by 90% by 2020. • 90% decrease in incidence may be possible (55% of simulations) if MAT and SSP also scaled-up. • 90% reduction by 2030 possible with no scale-up of harm reduction. • 159 treatments per 1000 PWID needed annually (24.9% of infections treated in first year). • Treatments halved (89 treatments, 14.5%) if MAT+SSP scaled-up. # Only a proportion of parameter sets achieved the target. * <5% of parameter sets achieved the target.

  25. Scenario Analysis Results NSP remains cost-effective even when HCV treatment is cheaper Increasing treatment increases cost-effectiveness of NSP

  26. Implications – mixture of evidence • Empirical evidence OST/NSP reduces HCV • NSP & OST highly cost-effective • Models suggest that: OST/NSP avert HCV transmission & increase impact of HCV TasP • Dynamic and Economic Models show that: • HCV treatment scale-up critical for HCV prevention • Early treatment of PWID cost-effective • NSP (and OST) highly cost-effective • Increasing HCV treatment increases NSP CE • No observed evidence (yet) of HCV TasP (in PWID)

  27. Implications – mixture of evidence • Model projections in Europe suggest treatment scale-up needed to observe change in HCV transmission • Uncertainty in measuring PWID prevalence & HCV incidence and prevalence • Strengthen PH surveillance so can detect change in prevalence & transmission • Promote HCV TasP and OST/NSP scale-up to prevent HCV transmission - EVALUATE • Trials and natural experiments

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