1. Epidemiology and Management of HCV in Injection Drug Users Patricia Perkins, MS, MPH Independent Healthcare Consultant San Francisco & Los Angeles, CA Advisory Board, OASIS, Oakland

2. HCV Infection Prevalence by Frequency of Selected Groups in the US Population Hemophilia patients 0 5 10 15 20 80 90 100 Percentage IVDU patients Dialysis patients STD patients Healthcare workers General population HCV Group Volunteer Blood Donors

3. HCV Prevalence NHANES 1988-1994

4. *Nosocomial, occupational, perinatal Remote (>15 yrs ago) Transfusion Sexual Other* Unknown Transfusion Injection Drug Use Unknown Other* Sexual Injection Drug Use Recent (=<15 yrs ago) Relative Importance of Risk Factors for Remote and Recent HCV Infection

5. Risk Factors for Transmission of Hepatitis Viruses and HIV Transfusion No Identified Risk Occupational Heterosexual partners MSM Injection drug use Risk Factor rare 30% 5-7%(past) 40% 15% 14%HBVPast 7- 20% 10% <<1% 20% 1% 60%HCV9% Past2% <<1% 10% 47% 31%HIV Percentage of Infections

6. Natural History of HCV 45-year cohort study (VAMC) in young military recruits 8,570 samples from 1948-1954 VAMC follow-up includes HCFA records Results: -- Anti-HCV = 17 (0.2%) -- Symptomatic liver disease unusual -- Liver-related death: 1/17 (6%) vs. 1.4% Source: Seef et al Ann Intern Med 2000; 132:105-11

7. 061218243036424854606672 0 20 40 60 80 100 Seroprevalence (%) Duration of Injecting (mo) HCV HBV HIV Risk of HCV, HBV, and HIV Infection Among Injection Drug Users Baltimore 1983–1988 Garfein RS. Am J Public Health. 1996;86:655. Garfein Part I

8. Risk of HCV Infection Among IDUs Garfein RS AJPH 1996; 86:655. Thorpe LE JID 2000;182:1588-94. Diaz T AJPH 2001; 91(1): 23-30. Baltimore: 1983-1988 Chicago: 1997-99 NY - Harlem: 1997-99 NY – LES: 1997-99 Garfein Part II

9. CDC Risk Reduction for IDUs If continuing to inject: Never reuse or share syringes, needles, or drug preparation equipment Vaccinate against hep B and hep A Refer to community-based risk reduction programs

10. The Issues of Hepatitis C Global Considerations The epidemiology of the infection and co morbid conditions Natural History variations Treatment; when, who and comorbidity Prevention – needles, sex, babies, adolescents Vaccines- delivery and effectiveness

11. Hepatitis C and Drug Use issues Drug interactions Virus species interactions How to treat out of treatment drug users Early Hepatitis C intervention (a set point?) Co morbid infections in pregnancy Liver under fire – Hep B & C, alcoholic hepatitis, stigma

12. Why Does Injection Drug Use Matter so Much with HCV? IDUs are largest group of infected persons in US and most of the West App. 1 million IDUs infected (mainly MMT and long-term IDU cohorts) Highest prevalence (85%+): both Coasts; Chi Highest incidence (10%-20%/annum: UFO Study (SF) & Seattle (RAVEN)

13. Natural History of Chronic HCV Summary Aging of HCV+ pt pool peaks in 10-20 yrs. * Decompensated cirrhosis * HCC (liver cancer) * Potential liver transplant candidates * Liver-related deaths Future healthcare cost burden is very high Treatment impact – Reduced liver decompensation and health costs – Best effect by treating more advanced disease (Fibrosis II+?) – Little societal public health effect from treating mild disease

14. Why Does Injection Drug Use Matter in HCV Transmission? Source of Most HCV transmission All drug use paraphernalia are implicated in its transmission: cookers, cottons, tie-ups Higher rate of transmission than HIV requires different type of risk reduction educ. Will require developing, testing, and implementing treatment strategies effective with drug users: (O.A.S.I.S. model)

15. Recommendations/Q's 6/02 NIH Consensus Dev't Conference Recommendations/Q's 6/02 NIH Consensus Dev't Conference Natural History of HCV in IDU's? – Not well understood (Thomas et al; JAMA 2000; Nov 22; 284 (20); 2592 Which patients should be treated? – Individual decisions by patients and clinicians – Balanced portrayal of risks and benefits – Drug use NOT a criterion for HCV treatment

16. Add'l Questions for Treatment of HCV+ Drug Users How should patients be treated? – Interdisciplinary approach: expertise in HCV & substance abuse; harm reduction models How should patients be monitored? – Assess; monitor, and support adherence and mental health (replicate HIV & TB successes) How can transmission be prevented? – Teach safer injection; e.g. CRC (Chi) & PHP (NYC) – use “safety kits”

17. What research is still needed for HCV+ IDUs/DUs? Effective treatment strategies for drug users in substance abuse treatment Developing tools for HCV recovery readiness for drug users NOT in drug treatment Behavioral modification and risk reduction around alcohol consumption

18. Recommendations by IDU/Infectious Disease Experts Which patients with HCV should be treated or even evaluated to point of treatment? – “HCV treatment decisions should be made by patients and their physicians on a case-by-case basis, factoring in risks, benefits, and personal values for each individual patient.” Edlin et al; NEJM 2001; 345: 211-4

19. Risk-Benefit Considerations For all Patients with HCV: Limited benefit (SVR < 50% in genotype 1) Side effects (physical & mental) Timing (future regimens) Need/urgency (disease stage, best on histology/biopsy

20. Risk Benefit cont. Clinical benefit not shown in IDUs in long- term follow-up studies Patients' personal values, feelings about infection/side effects – “Patients should receive a balanced portrayal of the risks and benefits of treatment”

21. Risk Benefit Considerations For IDUs with HCV: Adherence – IDUs CAN adhere to medical regimens (HIV/TB) – Physicians CANNOT predict patients' adherence Psychological side effects – No evidence to date of inordinate side effects in IDUs; driven more by previous hx of psych issues/depression

22. Risk Benefit, cont. Timing: – HCV and substance abuse CAN be treated together – No data on optimal sequence; current practice is for six months of MMT or abstinence-based treatment Re-infection: – Evidence suggests low risk, limited data

23. Models for Treatment Adherence: HIV Guidelines Assess readiness BEFORE prescribing Monitor adherence during therapy No patient should automatically be excluded Provide adherence support Source: Guidelines for Antiretroviral Agents: Recomm of the Panel on Clinical Practices for Treatment of HIV. MMWR 2002; 51 (RR-7)7: (http://www.cdc.gov/mmwr/mmwr_rr.html)

24. HCV Rx in IDUs Entering Opiate Detox (N = 50) Backmund, Hepatol 2001; 34: 188-93 Pts: Active opiate injectors beginning opiate detox RX: IFN or IFN/RBV MD's: expertise in HCV & substance abuse Patients who relaped: – Received MMT – Continued HCV meds despite drug use Instruction on HCV risk reduction while injecting drugs

25. Results for this Detox Study Overall SVR of 36% This is prior to use of Peg IFN products Only statistically significant predictor of greater SVR was among patients who kept greater than 67% of medical appointments Authors suggested role for social engagement with clinic as factor in adherence

26. MMT Patients treated for HCV in US: OASIS (n = 66) Pts: chronic MMT recipients – 6 centers Rx: IFN-alpha-2b + RBV Patients selected by adherence to clinic visits and support groups 62% pre-existing psychiatric disorder 21% drank alcohol during HCV treatment

27. MMT OASIS Study, cont. 30% used illicit drugs during HCV treatment No serious psychological side effects during HCV treatment 85% required antidepressants during tx. 39% required increase in methadone dose (minimum of 10 mg/day) Sylvestre, DDW (AASLD #118); Gastroenterology 2002; 122 (4 Suppl 1): A630

28. Recommendations Approach to Caring for IDUs & DU's – Education, counseling, support to avoid: Sharing syringes or disinfection?? Sharing other paraphernalia (cookers, cottons, etc) Any blood contact (e.g. giving/receiving injections) Access to sterile syringes: – Referral to SEPs, as applicable/where possible – Syringe Rx (now possible in NYS & Texas) Source: CDC fact sheet: (http://www.cdc.gov/idu/facts/physician.htm) (

29. Final NIH Consensus Statements Recommendations: 6/02 With Greatest Public Health Impact “Institute measures to reduce transmission of HCV among IDUs, including providing access to sterile syringes through needle exchange, physician prescription, and pharmacy sales; and expanding the Nation's capacity to provide treatment for substance abuse...”

30. Consensus, cont....”Physicians and pharmacists should be educated to recognize that providing IDUs with access to sterile syringes and education in safe injection practices may be lifesaving.”

31. Consensus Recomm, cont. “Encourage a comprehensive approach to promote the collaboration among health professionals concerned with management of addiction, primary care physicians, and specialists involved in various aspects of HCV to deal with the complex societal, medical, and psychiatric issues of IDUs afflicted by the disease.”

32. Acknowledgements Drs. Brian Edlin & Alex Kral, UCSF Urban Health Study Dr. Ian Williams, Hepatitis Branch, US CDC Dr. Richard Garfein, HIV Branch, US CDC Dr. Robert Gish & Dr. Ed Wakil, CPMC, SF