Implications of new hepatitis C treatments for WHO activities related to people who inject drugs

1. Implications of new hepatitis C treatments for WHO activities related to people who inject drugs Nicolas Clark, Medical Officer Management of Substance Use WHO, Geneva CREIDU Colloquium Melbourne 2014

2. Number of deaths/year from selected conditions, 2010 1.4 million people died in 2010 of viral hepatitis Source: Global Burden of Disease Study 2010 Lozano et al, Lancet 2012

3. Estimated annual deaths from selected causes by region, 2010 Source:Courtesy of IHME – Global Burden of Disease Study

4. Number of hepatitis deaths by virus type and disease outcome, 2010 Most deaths are due to chronic hepatitis B and C E Source: Global Burden of Disease Study 2010 Lozano et al, Lancet 2012

5. Global prevalence of hepatitis C infection, 2005 adults (19-49 years), by GBD region Source:Hannafiah et al. Hepatology 2013

6. Prevalence of HCV among persons who inject drugs • HCV prevalence in PWID >50% in most countries; between 60-80% in 25 countries • and >80% in 12 countries Nelson et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet, 378 (9791), 2011.

7. Drug use GBD 2010 estimates

8. Disease burden attributable to drug dependence by age in 2010 (Degenhardt et al, Lancet, 2013)

9. WHO's Hepatitis area of work: evolution… 2010 2011 2012 2013 2014 2015 (and beyond) World Health Assembly Resolution on Viral Hepatitis Establishment of Global Hepatitis Programme (GHP) Reorganization of Global Hepatitis Programme WHA resolution STAC-Hep Global Framework Implementation of Resolution And Global Action Plan • Hep B immunization • Blood/injection safety • Outbreak control • Water and sanitation

10. WHO's internal organization of the Global Hepatitis Programme HIV/AIDS (HIV) Pandemic and Epidemic Diseases (PED) Food Safety, Zoonoses and Foodborne Diseases (FOS) Service Delivery and Safety (SDS) Essential Medicines and Health Products (EMP) GHP Secretariat HQ Health Statistics and Information Systems (HSI) Management ofNoncommunicable Diseases (MND) Immunization, Vaccines and Biologicals (IVB) Mental Health and Substance Abuse (MSD) Regional Offices AFRO EURO SEARO AMRO EMRO WPRO Country Offices Country Offices

11. Global Hepatitis Framework: Goals • Within a health systems framework: • Reduce transmission • Reduce morbidity and mortality and improve treatment and care of patients • Reduce the socio-economic impact at individual, community and population levels • Entry-point to link with and support other critical organizational priorities, including • universal health coverage • affordable access to commodities • health inequities

12. Global Hepatitis Framework: Four Axes Axis 1: Partnerships, resource mobilization and communication Axis 2: Data for policy and action Axis 3: Prevention of virus transmission Axis 4: Screening, care and treatment

13. Axis 1: Increasing engagement through awareness, partnerships and mobilizing resources • Status: • Low levels of awareness, engagement, political action, financial commitment • Actions and plans: • Promotion of World Hepatitis Day commemoration • Establish Global Hepatitis Network • Global Hepatitis Policy Report • Global Partners’ meeting on hepatitis • Formation of civil-society reference group

14. World Hepatitis Day 2013 sample posters

15. WHO Global Policy Report 2013 • Aim: To assess WHO Member States' response to hepatitis – in the context of the WHO Resolution 63.18 • Conducted in collaboration with World Hepatitis Alliance • Response rate: 125 of 194 (64%)Member States

16. Axis 2: Evidence-based policy and data for action • Status: • Weak surveillance systems leading to poor quality of country-level data on burden of infection and disease outcomes • Lack of reporting system to monitor implementation of treatment scale-up • Actions: • Publish global prevalence and burden estimates for viral hepatitis • Develop guidelines for hepatitis surveillance in low- and middle-income countries

17. WHO sponsored systematic reviews of hepatitis prevalence data

18. Axis 2: Evidence-based policy and data for action • Plans: • Establish modelling reference group • Conduct regional adaptation workshops of surveillance guidance • Conduct country hepatitis burden-of-disease and national planning workshops • Develop a monitoring and reporting framework for assessing country and global hepatitis response

19. Axis 3: Prevention of virus transmission • Status: Effective prevention measures exist but level of implementation is variable • Actions: • Blood safety: • policy guidance and technical assistance to countries for • universal access to safe blood and blood products • self-sufficiency in safe blood and blood products based on voluntary unpaid blood donation • Injection safety: • SIGN Network • WHO-UNICEF-UNFPA for exclusive use of auto-disable syringes in immunization services • Promotion of harm-reduction guidance and services

20. Axis 3: Prevention of virus transmission • Plans: • Immunization: • Promotion of birth dose administration • Hepatitis E vaccine SAGE working group • Blood safety: • Continued emphasis on implementation of policies • Injection Safety: • Launch of Global Injection Safety Campaign

21. Axis 4: Treatment • Status: • Dramatic advances in treatment options • Very low levels of: • Awareness among general public and health-care workers • Access to screening • High-quality, low-cost diagnostics • Laboratory infrastructure • Treatment uptake • New WHO hepatitis treatment guidelines

23. WHO’s role in improving access to hepatitis therapy • Screening • Care • Treatment Treatment Guidelines Prequalification of generic medicines Essential Medicines List Advocacy, guidance and technical assistance for improved treatment access Multi-stakeholder engagement World Hepatitis Day observance Improved prevalence estimates Prequalification of diagnostics Screening/ testing guidelines

24. Topics for WHO hepatitis C screening, care and treatment guidelines Who should be tested for hepatitis C (antibodies)? When to confirm HCV infection (PCR)? When to start treatment? What medicines to use? What interventions to slow progression of liver disease? How to assess degree of liver fibrosis/cirrhosis? How to monitor for response to treatment and drug adverse reactions?

25. New Opportunities for treatment scale-up • Current treatment regimens are complex, costly (drugs and monitoring) and have significant toxicities • Dramatic new treatment results, high SVR rates, oral regimens, pan-genotype and high safety profile • WHO published it’s first ever hepatitis C treatment guidelines in April 2014 • Successful price reductions, • Egypt $900 for a 12 week course of sofosbuvir • USA $84,000 in comparison

26. WHO recommendations on diagnosis and treatment of hepatitis C in PWID • Screen PWID • anti-HCV antibodies • rapid testing vs serology • Diagnosis • HCV RNA • Reduce alcohol intake • Staging • liver biopsy • non – invasive test • Treatment • genotype 1,2,3,4 • sofosbuvir • pegylated interferon and ribavirin • genotype 1 • telaprovrevir or bocepravir • genotype 1b & 1a (without Q80K polymorphism) • simepravir

27. SVR in PWUD Aspinall et al. (2013)

28. Re-infection rates in PWUD Aspinall et al. (2013)

29. What can we learn from HIV about increasing services for PWID?

31. Inequitable access to ART Wolfe et al, The Lancet 2010; 376:355-66.

32. Integration and colocation of services

33. Policy guidelines for TB and HIV services for drug users Joint Planning Service providers National & local coordination body Plans with roles, responsibilities & M&E Human resources and training available Support to operational research Package of Care TB infection control plans in care settings Case finding protocols at services drug users present Treatment services for TB and HIV available Isoniazid prevention available HIV prevention (Harm Reduction Package) Overcoming Barriers Integrated services (Link TB/HIV treatment and harm reduction Equivalence of care in prisons Adherence support measures Comorbidity not to be used to withhold treatment

34. Overlapping Epidemics IDU Hepatitis HIV

35. Hepatitis ProgrammeDOTDiagnosis Staging Alcohol counselling Treatment monitoring Adherence SupportDrug Interactions CommunicationCollaboration CommunicationCollaboration Drug TreatmentOpioid Substitution TherapyEffective Counseling DOTUrine MonitoringDrug InteractionsSyringe Exchange HIV ProgramAntiretroviral Treatment Drug Interactions VCT Toxicity Monitoring Prophylaxis of OIs Adherence Support Secondary PreventionSyringe Exchange CommunicationCollaboration

36. models of care • non-integrated • referral • linkage • integrated care • integrated in general health care • primary care • multi-skilled team • specialist outreach • integrated in district hospital • integrated specialist services • hepatitis treatment provided in drug treatment • multiskilling or specialist outreach • drug treatment provided in hepatitis clinic • combined addiction and hepatitis specializations

37. Can any part of the health system treat hepatitis?

38. requirements for hepatitis treatment • laboratory capacity • serology • NAT/genotype/viral load • testing throughout treatment • reliable supply of medication • dispensing capacity • clinical skills • somewhat complicated treatment algorithms • potentially life threatening adverse events common

39. models of care • non-integrated • referral • linkage • integrated care • integrated in general health care • primary care • multi-skilled team • specialist outreach • integrated in district hospital • integrated specialist services • hepatitis treatment provided in drug treatment • multiskilling or specialist outreach • drug treatment provided in hepatitis clinic • combined addiction and hepatitis specializations

40. Hepatitis ProgrammeDOTDiagnosis Staging Alcohol counselling Treatment monitoring Adherence SupportDrug Interactions CommunicationCollaboration CommunicationCollaboration Drug TreatmentOpioid Substitution TherapyEffective Counseling DOTUrine MonitoringDrug InteractionsSyringe Exchange HIV ProgramAntiretroviral Treatment Drug Interactions VCT Toxicity Monitoring Prophylaxis of OIs Adherence Support Secondary PreventionSyringe Exchange CommunicationCollaboration

41. Case example - Ukraine • Before • example of OST / HIV / TB in Ukraine many years ago • OST on one side of town, HIV medication on another • no OST in TB hospital… • Now • multiple models of care • ARVs in narcology dispensaries • OST in HIV services • both ARV and OST in primary care and public hospitals

42. Collaboration of 150 NGOs, organised HCV treatment for co-infected individuals • Negotiated price reduction of interferon and ribavirin from $20,000 to $5,000 dollars per course • Decentralised approach • “Aids Clinic” • OST clinics • Community Clinics • Integrated into harm reduction/ART delivery. • Doctors providing the majority of care • Estimated to have treated 100 people, • Issues now with the political instability and clinics in Crimea and Eastern Ukraine have closed

43. Case example - Tanzania • Muhimbili medical centre • integrated treatment in an outbuilding of a district hospital • developed by infectious disease unit • integrated treatment: • drug dependence • HIV • TB • other conditions • daily dispensing: • methadone • ARV • TB treatment

44. ‘One-stop-shop’ Drug dependence treatment Family support Mental health care Drug user Overdose, HIV, Hepatitis prevention Social assistance & protection Antiretroviral therapy General health care

45. Current data on treating hepatitis in PWUD

47. Geographic distribution of models of care SCOTLAND 2 CANADA 4 NETHERLANDS 1 ENGLAND 3 UKRAINE 1 USA 14 SUISSE 1 ITALY 3 N.Z. 1 AUS 8

49. How to increase rates of adherence in treating PWUD • accessible • affordable • non judgemental • train staff in how to manage other issues faced by PWUD • psychosocial skills • encourage and provide OST for people who are opioid dependent • employ people with a history of drug use • work with the local drug using community • offer case management and outreach services

50. Other drug and alcohol activities at WHO • UNODC/WHO programme on drug dependence treatment and care • mhGAP programme on management of mental health, substance use and neurological conditions in non specialist settings