1. Specific issues and guidelines for HCV treatment in IDUs Bern d Schulte Centre for Interdisciplinary Addiction Research (CIAR), University Hamburg

2. Impact of clinical guidelines  Important tool for steering patients to medical treatment  Impact on allocation of resources and provision of therapy in terms of finances, qualification, and outreach.  Guidelines allowing/recommending treatment of a specific group facilitate access to care

3. HCV treatment in IDUs was/still is subject of controversy:  Assumption of poor adherence  Fear of additional adverse effects  Assumption of increased risk of reinfection  Reduced effectiveness

4. Medical adherence Disease: Lack of symptons, severity Medication Complexity, duration, side effects Patient and close relatives Knowlegde, self-care skills Demography/Sociodemography Education, financial resources Health care system Quality for & access to care; care organisation Specific issue: Adherence

5. Specific issue: Adherence in IDU I  Definition of adherence to HCV therapy: 80% of scheduled pegylated IFN-a and ribavirin doses 80% of the treatment period,  109 received treatment (74 HCV; 35 HCV/HIV), 75% ever reporting IDU  IDU prior to/during treatment did not impact 80/80 PEG-IFN adherence.  SVR was higher among those patients with ≥80/80 PEG-IFN adherence (67% vs. 35%, p=0.007) Grebely et al. (2011)

6. Specific issue: Adherence in IDUs II  Even severely opioid-dependent patients are possible candidates for HCV treatment:  27 patients in heroin maintenance treated for HCV  21 (81%) were retained in treatment  80/80 adherence rate was 92%.  18 (69%) achieved a sustained viral response (SVR) Schulte et al. (2010)

7. Specific issue: Adverse events  HCV treatment in "difficult-to-treat” patients (psychiatric patients n= 22, methadone patients n =18, former drug users n= 13)  Depressive nor psychotic symptoms differed significantly between groups during treatment  SVR 58.8% controls, 50% psychiatric patients, 72.2% methadone patients, 53.8% former drug users  Only genotype was associated with SVR Schäfer et al. (2007)

8. Specific issue: Reinfection  Clinician-related barrier: IDU relapse into drug injecting and re-infect after successful SVR  Low reinfection rates of were found, even in those who continued or relapsed into drug injecting: 0.8 to 4.7 per 100 person years  HCV reinfection after treatment may be cleared spontaneously  Risk counseling should be continued among IDU Grady et al. 2012

9. Specific issue: Effectiveness  Clinician-related barrier: Continuing reluctance to treat injection drug users (IDUs)  HCV treatment trials showing comparable SVR rates between IDUs and non-IDUs  Median SVR rate among IDUs: – 54.3% (range, 18.1%–94.1%) – 54%–63% in the large treatment trials Hellard et al. 2009

10. Specific issue: Effectiveness  Clinician-related barrier: Continuing reluctance to treat injection drug users (IDUs)  HCV treatment trials showing comparable SVR rates between IDUs and non-IDUs  Median SVR rate among IDUs: – 54.3% (range, 18.1%–94.1%) – 54%–63% in the large treatment trials Hellard et al. 2009

11. HCV lifecycle and possible therapeutic targets Conteduca et al. 2014

12. A brief history of SVR rates Strader & Seeff 2012

13. A brief history of HCV guidelines for IDUs 2004: Guidelines for HCV treatment in the EU and Norway Reimer et al. 2005

14. Why recommendations for PWID?  PWID population: advanced liver disease and liver-related mortality: 20–25% of deaths among HCV-infected individuals are from liver disease  High prevalence of HCV among PWID (65%), >80% among long-term PWID  High 12 months incidence rates: 5– 45%  Modelling studies suggest that implementation of HCV treatment for PWID could reduce transmission EASL,2014

15. International Network on Hepatitis in Substance User (INHSU)

16. Evidence Grading (Adapted from GRADE System) EvidenceNotesGrade High quality Further research is very unlikely to change confidence in the estimate of effect. A Moderate quality Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. B Low quality Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Any change of estimate is uncertain. C Recommendation NotesGrade Strong Factors influencing the strength of the recommendation included the quality of the evidence, presumed patient-important outcomes, and cost. 1 Weak Variability in preferences and values, or more uncertainty. Recommendation is made with less certainty, higher cost, or resource consumption. 2

17. Epidemiology and Prevention of HCV  PWID should be routinely and voluntarily tested for HCV antibodies/RNA and if negative, every 6–12 months (B1).  PWID should be provided with clean drug injecting equipment and access to OST as part of widespread comprehensive harm reduction programs, including in prisons (B1). Robaeys et al. 2013

18. Natural History of HCV & Effects of Drugs on the Liver  PWID should be counseled to moderate alcohol intake, or abstain if there is evidence of advanced liver disease (A1).  PWID should be counseled to moderate cannabis use, or abstain if there is evidence of advanced liver disease (B2).  The potential impact of drug use on the liver should be discussed with PWID (C2). Robaeys et al. 2013

19. Noninvasive Liver Fibrosis Assessment  Noninvasive assessments have a reduced risk and greater acceptance than liver biopsy, may enhance HCV screening and disease assessment among PWID, and should be offered, if available (B1).  Combining multiple noninvasive assessments is recommended, when possible (B1). Robaeys et al. 2013

20. Pretherapeutic Assessment  Pretherapeutic education should include discussions of HCV transmission, risk factors for fibrosis progression, treatment, reinfection risk, and harm reduction strategies (B1).  Pretherapeutic assessment should include an evaluation of housing, education, cultural issues, social functioning and support, finances, nutrition, and drug and alcohol use. PWID should be linked to social support services and peer support (A1). Robaeys et al. 2013

21. Impact of Drug Use on Adherence and SVR I  Adherence should consider missed doses and treatment discontinuation (B1).  PWID should be counseled on the importance of adherence in attaining SVR (A1).  HCV treatment can be considered for PWID, provided they wish to receive treatment and are able and willing to maintain regular appointments (A1). Robaeys et al. 2013

22. Impact of Drug Use on Adherence and SVR II  A history of IDU and recent drug use at treatment initiation are not associated with reduced SVR, and decisions to treat must be made on a case-by-case basis (B1).  PWID with ongoing social issues or history of psychiatric disease and those with more frequent drug use during therapy are at risk of lower adherence and SVR and need to be monitored closely during therapy (B1). Robaeys et al. 2013

23. Impact of Mental Health on Adherence and SVR I  Pretreatment assessment should include an evaluation of previous or current psychiatric illness, engagement with a drug and alcohol counselor or psychiatrist, and discussions around potential treatment options (A1).  If psychiatric comorbidities are present, decisions to treat with peg-IFN must be made on a case-by-case basis (A1). Robaeys et al. 2013

24. Impact of Mental Health on Adherence and SVR II  In cases of acute major and uncontrolled psychiatric disorders, a pretreatment psychiatric assessment is recommended (C2).  Prophylactic antidepressants are recommended in cases of a history of IFN-induced depression and with depressive symptoms at baseline (B1). Robaeys et al. 2013

25. Treatment Management  HCV treatment for PWID should be considered on an individualized basis and delivered within a multidisciplinary team setting (B1).  Access to harm reduction programs, social work, and social support services should be a component of HCV clinical management (B2).  Peer-based support should be evaluated as a means to improve HCV clinical management (B2). Robaeys et al. 2013

26. Reinfection Following Successful HCV Treatment  PWID should not be excluded from HCV treatment on the basis of perceived risk of reinfection (B1).  Harm reduction education/counseling should be pro- vided for PWID in the context of HCV treatment (B1).  Following SVR, monitoring for HCV reinfection through annual HCV RNA assessment should be undertaken on PWID with ongoing risk behavior (B2). Robaeys et al. 2013

27. Treatment of Acute HCV  PWID with acute HCV symptoms should be monitored for 12–16 weeks (incl. HCV RNA levels) to allow potential spontaneous clearance (A1).  Strategies to optimize adherence should be used in the setting of acute HCV, with consideration of directly observed therapy (B2). Robaeys et al. 2013

28. HIV/HCV Coinfection  HCV-infected PWID should be screened for HIV (B1).  The accelerated HCV disease progression in HIV/HCV should be considered in treatment decision making (B2).  Potential drug–drug interactions between HIV, HCV, and OST need to be considered (A1).  Early introduction of cART should be considered (B1). Robaeys et al. 2013

29. Management of Hepatitis B Virus Coinfection  PWID should be vaccinated for HAV and HBV (A1).  PWID with active HBV/HCV coinfection should be considered for peg-IFN/RBV therapy (B1). Robaeys et al. 2013

30. Thank you for your attention! B.Schulte@uke.de