1. HCV epidemiology: The knowns and the unknowns Margaret Hellard Burnet Institute, Melbourne

2. Disclosures I receive fellowship support from the National Health and Medical Research Council (Australia). The Burnet Institute receives infrastructure support from the Victorian Government Operational Infrastructure Fund. Gilead Science Abbvie BMS

3. A personal perspective – the knowns. Treatment works People want treatment It can stop deaths It can stop transmission Treatment can be cheaper

4. And the unknowns – or what I don’t understand …. Why any one thinks treatment should not be available to everyone Why treatments are not be made available to everyone How long we have to wait for common sense to prevail

5. Current trends worldwide: Implications for elimination Margaret Hellard Burnet Institute, Melbourne

6. Current trends HCV epidemiology - a brief overview. Elimination –WHO elimination targets –Why HCV elimination is possible in theory Barriers to achieving elimination –Cost of treatment –Restricted treatment access –Many people not diagnosed and those who are not in care –Prevention – not enough coverage Putting HCV elimination into practice And a couple of extra thoughts

7. HCV epidemiology – total HCV infections Total global prevalence - anti-HCV 1.6% or 115 million past viraemic infections – mostly in adults RNA positive - 1.1% ~ 80 million viraemic infections Estimated annual deaths – 800 million – and likely to increase if nothing changes Gower J Hepatol 2014

8. Distribution of HCV in adults using available data and extrapolations Gower J Hepatol 2014

9. Prevalence of HCV among persons who inject drugs Estimated 67% of people who inject drugs having been infected with HCV. Nelson et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet, 378 (9791), 2011.

10. HCV/HIV coinfection - men who have sex with men Platt et al 2016

11. HCV/HIV coinfection – people who inject drugs Platt et al 2016

12. Post-2015 Development Agenda Sustainable Development Goals (SDGs) Goal 3. Ensure healthy lives and promote well-being for all at all ages 3.3 By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases Universal health coverage - another key component of the SDGs - achieved when all people receive the health services they need, which are of sufficient quality to make a difference, without those people incurring financial hardship.

13. WHO Vision: A world where viral hepatitis transmission is stopped and everyone living with hepatitis has access to safe, affordable and effective care and treatment. Goal: Eliminate viral hepatitis as a major public health threat by 2030.

14. Proposed WHO targets for reducing new infections and stopping deaths

15. Achieving the 2030 targets Diagnosis 90% of chronic infections diagnosed Treatment 80% of eligible persons with chronic HCV treated Harm reduction Number of sterile needles and syringes provided per person who injects drugs per year - increase from 20 to 300. Estimated to be 75% coverage I can’t see a specific number for increasing coverage for opioid substitution therapy

16. A model that suggested HCV elimination was possible 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 Martin et al. J Hepatology 2011; J Theoretical Biology 2011

17. Martin et al. J Hep 2011 Prevention impact results: prevalence reductions at 10 years

19. HCV prevalence remains at over 30% in 2030 if only treat advanced disease

20. Treating PWID and advanced disease (for only five years) – stop deaths but also HCV prevalence < 10%

21. Why HCV elimination has become achievable Treatment with direct acting antivirals without pegylated interferon Simpler, safer and more effective

22. Can we achieve elimination by 2030? Only possible if all people with HCV infection can access to DAAs

23. Cost and treatment access Sofosbuvir US$84,000 SOF+LDV US$96,000 Simeprevir US$60,000 but on PBS in Australia Manufacturing costs (excluding R&D) A Hill, and G Cooke Science 2014;345:141-142

24. Barua et al Ann Int Med 2015

25. In countries where the epidemic is driven by PWID – need high quality harm reduction

26. Needle and syringe programs and OST work Multisite study of PWIDs across the UK OST and high coverage NSP (>100%) reduced an individuals risk acquiring HCV in isolation by half combination by ~80% Turner et al Addiction 2012

27. Evidence of protective effect of OST on HCV incidence in PWID Incidence w/out OST † Incidence w/OST † aHR or aOR (95% CI) Setting Sydney, AU 1 26.9 (14.5-50.0)3.3 (1.1, 10.2)0.18 (0.04-0.77) Vancouver, CA 2 5.5 (4.7-6.4)0.5 (0.3, 0.9)0.47 (0.29-0.76) San Francisco, US 3 28.2 (23.9, 33.4)8.6 (4.1, 18.1)0.39 (0.18-0.87) † HCV incidence per 100 PY for PWID without or with OST in last time period except for Vancouver study where HCV incidence per 100 PY is for PWID never and ever on OST 1.White et al. Opioid substitution treatment protects against hepatitis C virus acquisition in people who inject drugs: The HITS-c study. Med J Aust, 2014. 2.Nolan S et al. The impact of methadone maintenance therapy on hepatitis C incidence among illicit drug users. Addiction, 2014. 3.Tsui et al. Association of opioid agonist therapy with lower incidence of hepatitis C virus infection in young adult injection drug users. JAMA Intern Med, 2014.

28. Needle and Syringe Program Present in 82 countries Absent in 69 countries where IDU has been documented Globally, only 22 needles-syringes (range 12-42) are distributed per PWID per year Source: Reference Group to the United Nations on HIV and Injecting Drug Use 2010

29. Opioid substitution therapy (OST) Present in 75 countries Absent in 76 countries where IDU occurs Globally only 8/100 PWID (range 6-12) in receipt of OST Source: Reference Group to the United Nations on HIV and Injecting Drug Use 2010

30. Many countries - epidemic is due to poor blood safety or infection control - formal and informal WHO Global Strategy 2016-2021

31. Egypt – an example of this Initial epidemic – unsafe medical practices in schistosomiasis treatment program in 1950s - 1980s Ongoing new infections – ~165,000 annually – infusions, stiches, dental care, interfamilial transmission Initial phase of Egyptian response focused on increased treatment –over 200,000 started on treatment since role out in 2014 Most recent phase – recognition of importance of prevention Prevention action plan launched October 2014 2014 – 2018 – highlights the importance of prevention Components include surveillance, infection controls, blood safety, screening, care and treatment

32. Need to increase HCV testing in people at risk Dore GJ et al, J Viral Hep 2014

33. Increase testing – both screening and confirmation

34. Not enough people are being treated overall Need to increase access to care and think about where care is provided Holmberg NEJM 2013

35. Measures of fibrosis APRI Fibroscan - t ransient elastography Fibrotest FIB-4

36. There is no one “best” model of care

37. A snap shot of progress towards elimination

38. Georgia Around 3.7 million people; HCV prevalence ~5.16% Mixed epidemic April 2015 – Georgian government launched a plan to eliminate hepatitis C by 2020 Sofosbuvir supplied by Gilead Strategic plan 1.Raise awareness of viral hepatitis 2.Monitor health sector response to hepatitis 3.Prevent transmission of viral hepatitis in the community and health care settings 4.Reduce new infections and deaths due to viral hepatitis through expanded screening and treatment

39. Elaboration of the HCV Elimination Strategy Intersector al working group coordinate d by NCDC HCV screening, treatment and care Infection control Communi -cation Safe BloodSurveillance Laboratory Harm reduction Technical Advisory Group (TAG) of international experts reviewed and discussed the draft strategy and recommendations from the TAG were incorporated in the strategy

40. Activities in 2016 and Beyond February, 2016 Harvoni is introduced in the national elimination programme April, 2016 3rd National Workshop on Hepatitis C, Tbilisi, Georgia: 1. Present final results of serosurvey; 2. Discuss the 1st phase results; 3. Review of final HCV Elimination Strategy 2016-2020 Treatment of >20,000 patients per year with new DAAs

41. Iceland Ministry of Health announces HCV elimination – 7 th October 2015; sofosbuvir/ledipasvir provided by Gilead. HCV prevalence – 0.3% Approximately 800 – 1000 people with chronic HCV infection Mostly history of IDU Trap HepC - Aim of the program is to significantly reduce the rate of HCV transmission and diease burden and possibly eliminate the disease in Iceland Aim is to do this over next two years with ‚mopping up in the third First patients entered the program in January 2016. Treatment initiated for 200 patients every 4 months

42. Australia Available through PBS from 1 March 2016 –Available to everyone regardless of level of fibrosis or how you became infected or whether you currently inject drugs –Treatment available in tertiary hospital, community settings and prisons

43. Number of people who have commenced HCV treatment in Australia March to May 2016 – 11 216 patients’ initial prescriptions were processed; ~ 17 870 individuals started treatment (extrapolation on data taking into account time lag in reporting for reimbursement) Approximately 8% of total number of people living with chronic HCV in Australia Majority were prescribed sofosbuvir/ledipasvir (58%) followed by sofosbuvir/daclatasvir (38%) Kirby Institute Report June 2016

44. Elimination of HCV transmission in PWID Treat 58/1000 PWID – an estimated 4636 PWID in Australia – annually – prevalence falls to less than 10%

45. Egypt Presidential initiative to treat all Egyptians infected with HCV by 2018! Many challenges –Fragmented health system and competing organisations and NGOs to take the upper hand in funding support to find and treat more patients –Screening strategies and finding undiagnosed cases –Quality assurance of generics

46. HCV Elimination Community Coalition and Participation with grass root level organizations Community and civil society empowerment Use principles of social marketing and mobilization Access of hepatitis patients to treatment and care Establishment of Surveillance system Project Strategy:

47. Think local, act global - the role of the social network in HCV elimination. Hellard et al Hepatology 2014: Hellard et al JECH 2016

48. Treating injecting networks Modelling the impact of treatment on prevalence at 10 years; 80% SVR Hellard et al Hepatology 2014

49. Egypt – targeting people with high number of injections and whole villages

50. Target population >12 years =3573 Total Screened by Rapid test= 3500 Confirmed PCR +ve cases = 270 Prevalence rate >12 years: 7.71 % Insurance system 26 187,200 L.E. 21,355.78 EUR ELRIA H 189 155,240.06 EUR 1,360,800 L.E. Postponed by Medical examination & Investigations 55 Refusal Dropout%=2.04% (73 person) Treatment cost

51. HIV/HCV coinfection in gay and bisexual men Martin et al CID 2016 Scott et al – in preparation

52. Hepatitis C Vaccine Epidemic varies between countries – for some a vaccine will be vital In some countries – unlikely to have high quality harm reduction any time soon Even in countries with high treatment coverage – models show HCV vaccine would be effective in stopping reinfection.

53. Relative prevalence reduction of HCV after 15 years when treating 20/1000 PWID annually A.Vaccinate after treatment B.Vaccinate same number of people but randomly C.Vaccinate everyone not infected Scott el al BMC Med 2015 in press

54. Stigma and discrimination

56. Elimination of hepatitis C – requires a strategic multipronged approach Increased testing High quality harm reduction Improved quality of health services – formal and informal Increased access to treatment A vaccine Reduction in stigma and discrimination

57. Acknowledgements: Burnet Institute and Alfred Hospital –Paul Dietze, Peter Higgs, Joe Doyle, Amanda Wade, Nick Scott, Rachel Sacks Davis, Emma McBryde, David Iser, and all the field teams and others in the Viral Hepatitis Group and Drugs and Alcohol Group St Vincent’s Hospital – Alex Thompson, David Iser Kirby Institute – Greg Dore and team Bristol University & UCSD – Peter Vickerman and Natasha Martin WHO – Stefan Wiktor, Philippa Easterbrook and the Viral Hepatitis team CDC – John Ward Georgia NCDC and others - Ketevan Stvilia, Maia Butsashvili Egypt – Manal El-Sayed and Ammal Moktar Metwally Iceland - Sigurður Ólafsson