1. Management of Hepatitis C in Alcohol and Other Drug Services Greg Dore Viral Hepatitis Clinical Research Program National Centre in HIV Epidemiology and Clinical Research

2. Overview HCV epidemiology HCV treatment HCV treatment among methadone clients and current IDU Strategies to improve HCV treatment outcomes Hepatitis C management in AOD services

3. Hepatitis C epidemiology Hepatitis C notifications: 1990-2005 NCHECR 2006

4. Hepatitis C notifications 15-19 years: 1996-2005 Hepatitis C epidemiology NCHECR 2006 Heroin shortage

5. HCV prevalence among IDUs in annual NSP survey NCHECR 2006 % Hepatitis C epidemiology

6. HCV prevalence among IDUs in NSP survey (< 20 years) NCHECR 2006 % Hepatitis C epidemiology

7. HCV HIV HBV 264,000 90,000 – 160,000 17,000 Estimates of BBV prevalence in Australia Hepatitis C epidemiology

8. ORT 40,000 HCV RNA+ 20,000 HCV Ab+ 30,000 Estimates of HCV population on opiate pharmacotherapy Hepatitis C epidemiology

9. HBV and HCV stand. mortality rates: NSW linkage study Amin et al Lancet 2006 Hepatitis C epidemiology

10. Drug and liver-related deaths in people with HCV Deaths Hepatitis C epidemiology

11. Trends in HCV deaths: NSW linkage study Hepatitis C epidemiology

12. Estimates of people with HCV cirrhosis: 1990-2020 Dore et al J Clin Virol 2003 Hepatitis C epidemiology

13. IFN-α2b 24 weeks 8%-12% PEG-IFN 48 weeks 25%-29% IFN-α2b 48 weeks 15%-22% IFN-α2b+RBV 48 weeks 41% PEG-IFN+RBV 24-48 weeks 61%-65% 10 years Sustained Virological Response Hepatitis C treatment ?

14. Issues Positive Curative potential (50 – 80%) Improving response rates and clinical experience Government-subsidized Some expansion of access – removal of liver biopsy Negative Toxicity: flu-like symptoms, depression, anaemia, lethargy Requirement for contraception during and 6 months following Re-emergence of guilt, shame for some, and ongoing stigma Tertiary hospital – focused Hepatitis C treatment

15. PEG/RBV HCV treatment (sales): Mar 2005 – Nov 2006 Hepatitis C treatment Removal of mandatory liver biopsy patients

16. Sustained virological response (PEG-IFN-α2a/RBV) Fried et al NEJM 2002 % 29% 44% 65% Hepatitis C treatment

17. SVR for HCV genotype 1 % 21% 36% 46% Fried et al NEJM 2002 Hepatitis C treatment

18. SVR for HCV genotype 2,3 % 45% 61% 76% Fried et al NEJM 2002 Hepatitis C treatment

19. SVR rates in AOD service settings % Hepatitis C treatment

20. Impact of IDU status on HCV referral Stoove et al Drug & Alcohol Depend 2005 % Hepatitis C treatment

21. Impact of IDU status on HCV treatment Stoove et al Drug & Alcohol Depend 2005 % Hepatitis C treatment

22. HCV treatment consideration (Rankin Court / KRC, n=100) Doab et al CID 2005 % Hepatitis C treatment

23. Factors to consider in treatment decision-making Prognosis / stage of liver disease Efficacy of treatment Toxicity of treatment Presence of co-morbidities Stage of opiate dependency treatment Work and Family Treatment eligibility Hepatitis C treatment

24. Treatment eligibility (S100 Criteria) 18 years or older No evidence of de-compensated cirrhosis Chronic HCV infection Use of dual contraception if potential for pregnancy No prior IFN-based HCV treatment Hepatitis C treatment

25. IDU on drug treatment (n=237) Referral criteria -ve (n=58) Chronic HCV (n=121) HCV positive (n=178, 75%) Referral criteria +ve (n=63) Referred to clinic (n=43) Attended clinic (n=27) HCV referral and treatment (Byrne Surgery, Redfern) HCV treatment (n=14) Referral criteria: >10 years duration of HCV ALT elevation Clinical evidence of cirrhosis Hepatitis C treatment Hallinan R et al Drug & Alcohol Dependence 2007

26. PatientHCV genotypeFibrosis stageHCV treatment / outcome 58M1NAPEG/RBV ceased, no EVR 38F3a3PEG/RBV completed, ETR 42M1/3a4 (cirrhosis)PEG/RBV completed, SVR 29M3a2PEG/RBV completed, SVR 37M3a2PEG/RBV completed, SVR 39M3a4 (cirrhosis)PEG/RBV completed, SVR 43M3a3PEG/RBV completed, SVR 39M2a/2c4 (cirrhosis)PEG/RBV completed, SVR 33M3a3PEG/RBV completed, ETR 44M3a3PEG/RBV commenced, EVR 44M3a3PEG/RBV commenced 45M3a2PEG/RBV commenced 33M3aNAPEG/RBV commenced HCV treatment (Byrne Surgery, Redfern) Hepatitis C treatment

27. Improving HCV treatment uptake and outcomes HCV screening and treatment clinics in D&A treatment settings Education and training of AOD HCWs in HCV treatment Education and training of HCV treatment HCWs in AOD Research on models of treatment delivery New therapeutic agents with greater efficacy, reduced toxicity, and shortened duration of therapy Hepatitis C treatment

28. 1 2 3 4 5 6 7 01234567891011121314 Study Time (in Days) Median HCV RNA (Log 10 IU/mL) PlaceboVX-950 450 mg q8hVX-950 750 mg q8h VX-950 1250 mg q12h Reesink et al DDW. 2005. Protease Inhibitor: VX 950 Advances in HCV Therapy

29. Week 0 12 24 36 48 72 Phase II studies with Telaprevir (PROVE 1 and 2): HCV genotype 1 PEG/RBV PEG D C B A TPV PEG/RBV E Advances in HCV Therapy

30. PROVE studies (Telaprevir) interim efficacy analysis (week 12) % Vertex press release Dec 13, 2006 Advances in HCV Therapy

31. Histamine Hcl Levovirin Phase II On market Phase III Phase I Research Preclinical Protease inhibitors HCV vaccines Other IFNs IFN & PEG-IFN Many others including Antisense Antifibrotics Immune stimulants Gene therapy Ribozymes Ribavirin Polymerase inhibitors Antisense HCV immunotherapy Viramidine IL 10 & IL 12 Others Apoptosis inhibitors Therapies in development Hepatitis C treatment