The Challenge of Addiction and Hepatitis C Diana Sylvestre, MD University of CA, San Francisco OASIS
HCV Prevalence by Selected Groups United States Hemophilia Injection drug users Surgeons, PSWs* Hemodialysis   Average Per...
Injecting Drug Use and HCV Transmission <ul><li>Highly efficient </li></ul><ul><ul><li>Contamination of drug paraphernalia...
Relative Importance of Risk Factors for Hepatitis C Adapted from CDC Hepatitis Slide Kit  http:// www.cdc.gov/ncidod/disea...
“ Drug Users” are heterogeneous Cannabis Methamphetamine Cocaine Heroin Regular use Binge use Polysubstance use Intermitte...
The evidence for addiction as a brain disease <ul><li>Dopamine release in the Nucleus Accumbens is a common  characteristi...
Treatment options for depression <ul><li>Tricyclics (TCAs) </li></ul><ul><ul><li>Amitriptyline, imipramine, nortriptyline,...
Treatment options for addiction <ul><li>Alcohol </li></ul><ul><ul><li>Disulfiram, acamprosate, naltrexone </li></ul></ul><...
Heroin-associated Mortality Hser, Y. I., et al. (2001)  Arch Gen Psychiatry , 58, 503-8.
Progression of Liver Fibrosis Among IDUs With Chronic HCV <ul><li>119 prospectively followed IDUs </li></ul><ul><li>Demogr...
<ul><li>“HCV therapy has been successful even when the patients have not abstained from continued drug or alcohol use... T...
The data As it exists….
HCV Treatment in Methadone Patients P  = NS 36 53 24 40 Overall SVR Relapsed  and Returned to Treatment Relapsed  and Did ...
Attendance predicts SVR Backmund M, et al.  Hepatology. 2001;34:188-193. 45 6 0 20 40 60 80 100 >2/3 Appts <2/3 Appts SVR,...
Mauss, et al.  (Hepatology, 2004) p=0.16 n=50 n=50
HCV Treatment in the  Setting of Active Drug Use 0 48 31 7.6 61 50 Noncompliance End of  Treatment Response SVR Patients (...
SVR Rate May Increase with Abstinence ≥  6 mo < 6 mo None Occasional Regular Abstinence Duration Substance Use 22 30 35 21...
Protective Immunity? <ul><li>Dove L, Phung Y, Bzowej N, Kim M, Monto A, Wright TL. Viral evolution of hepatitis C in injec...
Current Studies at OASIS
A Brief HCV Prevention Education Intervention for In- and Out-of-Treatment Drug Users CDC U50/CCU923257
 
 
Protocol <ul><li>Two test populations, two video curricula: </li></ul><ul><ul><li>Out of treatment drug users at syringe e...
Protocol <ul><li>Demographic/risk behavior questionnaire </li></ul><ul><li>Randomization: </li></ul><ul><ul><li>Usual care...
Sample Knowledge Questions: SEP <ul><li>Which of the following can transmit HCV infection? (MC) </li></ul><ul><li>How ofte...
Preliminary Results
Demographics 67% 59% Told HCV+ 72% 84% Tested for HCV 98% 97% Tested for HIV 42% 23% 1 0  care in ER 41% 30% Uninsured 26%...
Demographics 19% 28% Tattoo in jail 51% 38% Prev STD 45% 13% > 3 sex partners <1yr 29% 34% Always condom 46% 58% Never con...
SEP Knowledge 33 21 30 41 40 n 29 30 23 ** ** ** ** ** P<0.001 for difference from usual care at all time points
MMT Knowledge Scores 84 85 52 68 47 73 53 43 n 36 ** P<0.001 for difference from usual care at all time points ** ** ** **...
MMT Attitudes/Motivation 46 43 85 68 52 84 64 55 36 n p=0.02 p=0.01 p=0.19 * * * *
Transitioning Street-Recruited Heroin Users to HCV Treatment using Buprenorphine NIDA DA015629-01
Study Design Street-recruited  Heroin Users Hepatitis C Viral Testing Active: 12-24 weeks  buprenorphine Inactive: Ineligi...
Enrollment <ul><li>All screened = 415 </li></ul><ul><li>Eligible = 275 </li></ul><ul><ul><li>Ineligible =  140 (33%) </li>...
Relevance All Screened: n=415 n = 275 n = 188 n = 146
The study sample is representative NS 19.2% 23.4% 23.6% 23.9% Latino NS 41.8% 39.4% 40.0% 37.3% Black NS 33.6% 31.9% 32.0%...
*Significant for the difference between screened and eligible cohorts The study sample is representative NS 55.5 60.1 50.3...
Drug Use Week 0-12
Treatment Retention (n=146) 58% 45%
Interest in HCV Treatment (n=146) Early Bupe termination Chose HCV Tx Chose taper
HCV Treatment Outcomes <ul><li>Completed treatment, n=37 </li></ul><ul><li>Early termination, n=18 </li></ul><ul><ul><li>3...
Outcomes by Genotype 37 10 26 21 13 7 32 11 20
Relevance to heroin users who initiate buprenorphine
Relevance to all eligible heroin users
OASIS Resources <ul><li>Providers: </li></ul><ul><ul><li>Hepatitis C University </li></ul></ul><ul><ul><ul><li>www.hcvu.or...
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The Challenge of Addiction and Hepatitis C (pps)

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  • NS, nonsignificant; SVR, sustained virologic response Sustained response is possible in patients who abuse drugs but are in rehabilitation, as demonstrated by Backmund and colleagues. However, relapse is possible and patients should be informed of this.
  • SVR, sustained virologic response.
  • IDU, injection drug use; NS, nonsignificant; SVR, sustained virologic response Robaeys and colleagues reported that active vs nonactive intravenous drug users had similar rates of noncompliance, end-of-treatment response, and SVR. Although active drug use may not be an absolute contraindication to therapy, the possibility of reinfection is a concern should intravenous drug activity continue after therapy.
  • SVR, sustained virologic response Sylvestre and colleagues have extensively studied methadone patients and have reported that patients with regular exposure to illicit drugs do not achieve SVR vs those who occasionally or never indulge. A period of abstinence greater than 6 months also suggests an improvement in SVR, although this may not be statistically significant. What is the effect on clinical implementation of hepatitis C therapy? In patients who are actively using intravenous drugs, therapy is not contraindicated but may be counterproductive due to the risk of noncompliance and drug use acceleration. However, patients who only occasionally use illicit drugs or have complete abstinence from them can be considered for therapy. The duration of abstinence remains controversial and should be discussed with the patient.
  • The Challenge of Addiction and Hepatitis C (pps)

    1. 1. The Challenge of Addiction and Hepatitis C Diana Sylvestre, MD University of CA, San Francisco OASIS
    2. 2. HCV Prevalence by Selected Groups United States Hemophilia Injection drug users Surgeons, PSWs* Hemodialysis Average Percent Anti-HCV Positive Gen population adults Military personnel STD clients Pregnant women * PSWs (personal-service workers) are individuals whose occupations involve close personal contact with clients (e.g., hairdressers, barbers, estheticians, cosmetologists, manicurists, pedicurists, massage therapists). Adapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset. HIV patients
    3. 3. Injecting Drug Use and HCV Transmission <ul><li>Highly efficient </li></ul><ul><ul><li>Contamination of drug paraphernalia, not just needles and syringes </li></ul></ul><ul><li>Rapidly acquired after initiation </li></ul><ul><ul><li>30% prevalence after 3 years </li></ul></ul><ul><ul><li>>50% prevalence after 5 years </li></ul></ul><ul><li>Four times more common than HIV </li></ul>Adapted from CDC Hepatitis Slide Kit.
    4. 4. Relative Importance of Risk Factors for Hepatitis C Adapted from CDC Hepatitis Slide Kit http:// www.cdc.gov/ncidod/diseases/hepatitis/slideset Remote (>15 yrs ago) Recent (<15 yrs ago) Transfusion Sexual Other* Unknown Transfusion Injection Drug Use Unknown Other* Sexual Injection Drug Use * Nosocomial, occupational, perinatal
    5. 5. “ Drug Users” are heterogeneous Cannabis Methamphetamine Cocaine Heroin Regular use Binge use Polysubstance use Intermittent use Injection Intra-nasal Oral
    6. 6. The evidence for addiction as a brain disease <ul><li>Dopamine release in the Nucleus Accumbens is a common characteristic of virtually every drug of abuse. </li></ul>Koob, Trends in Pharm Sci, ,1992 DMT VTA LC Frontal Cx N. Acc Hippo AMG
    7. 7. Treatment options for depression <ul><li>Tricyclics (TCAs) </li></ul><ul><ul><li>Amitriptyline, imipramine, nortriptyline, etc. </li></ul></ul><ul><li>Monoamine oxidase inhibitors (MAOIs) </li></ul><ul><ul><li>Phenelzine, tranylcypromine, isocarboxazid, etc. </li></ul></ul><ul><li>Selective serotonin reuptake inhibitors (SSRIs) </li></ul><ul><ul><li>Fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, etc. </li></ul></ul><ul><li>Serotonin antagonists </li></ul><ul><ul><li>Trazodone, nefazodone </li></ul></ul><ul><li>Other agents </li></ul><ul><ul><li>Bupropion, venlafaxine, mirtazapine, reboxetine, etc. </li></ul></ul>
    8. 8. Treatment options for addiction <ul><li>Alcohol </li></ul><ul><ul><li>Disulfiram, acamprosate, naltrexone </li></ul></ul><ul><li>Opiate </li></ul><ul><ul><li>Methadone, buprenorphine, naltrexone </li></ul></ul><ul><li>Stimulants </li></ul><ul><ul><li>? </li></ul></ul>
    9. 9. Heroin-associated Mortality Hser, Y. I., et al. (2001) Arch Gen Psychiatry , 58, 503-8.
    10. 10. Progression of Liver Fibrosis Among IDUs With Chronic HCV <ul><li>119 prospectively followed IDUs </li></ul><ul><li>Demographics </li></ul><ul><ul><li>96% were African American </li></ul></ul><ul><ul><li>97% HCV genotype 1 </li></ul></ul><ul><ul><li>27% HIV-infected </li></ul></ul><ul><ul><li>Median age 42 years. </li></ul></ul><ul><li>After 4.2 years median follow-up 21% had progression of fibrosis </li></ul>Wilson LE, et al. Hepatology. 2006 Apr;43(4):788-95. Significant Fibrosis 9.3% Insignificant Fibrosis 90.7% Significant fibrosis was defined as modified Ishak score 3 or greater, and progression of fibrosis was defined as an increase 2 or more units or clinical evidence of end-stage liver disease. Significant fibrosis at first biopsy:
    11. 11. <ul><li>“HCV therapy has been successful even when the patients have not abstained from continued drug or alcohol use... Thus, it is recommended that treatment of active injection drug use be considered on a case-by-case basis, and that active injection drug use in and of itself not be used to exclude such patients from antiviral therapy.” --NIH Consensus Statement on HCV, 2002 </li></ul>
    12. 12. The data As it exists….
    13. 13. HCV Treatment in Methadone Patients P = NS 36 53 24 40 Overall SVR Relapsed and Returned to Treatment Relapsed and Did Not Return to Treatment Did Not Relapse Backmund M, et al. Hepatology. 2001;34:188-193. 0 20 40 60 80 100 Patients (%) SVR Rates in Injection Drug Users in Detox (N = 50) n=10 n=15 n=25
    14. 14. Attendance predicts SVR Backmund M, et al. Hepatology. 2001;34:188-193. 45 6 0 20 40 60 80 100 >2/3 Appts <2/3 Appts SVR, % n=12 n=38 P <0.05
    15. 15. Mauss, et al. (Hepatology, 2004) p=0.16 n=50 n=50
    16. 16. HCV Treatment in the Setting of Active Drug Use 0 48 31 7.6 61 50 Noncompliance End of Treatment Response SVR Patients (%) Active IDUs Nonactive IDUs P = NS HCV Treatment Outcomes: Active IDUs vs Nonactive IDUs (N = 406) Robaeys G, et al. Eur J Gastroenterol Hepatol. 2005;18:159-166. 0 20 40 60 80 100 P = NS P = NS
    17. 17. SVR Rate May Increase with Abstinence ≥ 6 mo < 6 mo None Occasional Regular Abstinence Duration Substance Use 22 30 35 21 0 Sylvestre DL, et al. J Subst Abuse Treatment. 2005;29:159-165. 10 20 30 40 Sustained Virologic Response (%) Degree of Drug Use and SVR (N = 76) 0 P = .18 P = .09
    18. 18. Protective Immunity? <ul><li>Dove L, Phung Y, Bzowej N, Kim M, Monto A, Wright TL. Viral evolution of hepatitis C in injection drug users. J Viral Hepat. 2005 Nov;12(6):574-83. </li></ul><ul><li>Grebely J, Conway B, Raffa JD, Lai C, Krajden M, Tyndall MW. Hepatitis C virus reinfection in injection drug users. Hepatology. 2006 Nov;44(5):1139-45. </li></ul><ul><li>Currie S, Tracy D, Ryan J, Belaye T, Kim M, Monto A. Injection drug users who resolve the HCV virus appear to be protected from reinfection. AASLD 2006: 167A. </li></ul>Patients with ongoing or prior HCV infection may develop immunity that protects against further infection with HCV despite repeated exposure
    19. 19. Current Studies at OASIS
    20. 20. A Brief HCV Prevention Education Intervention for In- and Out-of-Treatment Drug Users CDC U50/CCU923257
    21. 23. Protocol <ul><li>Two test populations, two video curricula: </li></ul><ul><ul><li>Out of treatment drug users at syringe exchange, n=100 </li></ul></ul><ul><ul><ul><li>Brief, 7-minute peer-based prevention education video </li></ul></ul></ul><ul><ul><li>In-treatment drug users enrolled in methadone maintenance, n=450 </li></ul></ul><ul><ul><ul><li>30 minute peer based education video </li></ul></ul></ul><ul><ul><ul><ul><li>Two viewing formats: single session vs. 4 session </li></ul></ul></ul></ul>
    22. 24. Protocol <ul><li>Demographic/risk behavior questionnaire </li></ul><ul><li>Randomization: </li></ul><ul><ul><li>Usual care vs. video intervention </li></ul></ul><ul><ul><ul><li>SEP 1:1 </li></ul></ul></ul><ul><ul><ul><li>MMT 1:1:1 (1 usual care: 1 single session: 1 4-part viewing) </li></ul></ul></ul><ul><li>KAM test (Knowledge/Attitudes/Motivations) </li></ul><ul><ul><li>Baseline </li></ul></ul><ul><ul><li>Immediate post video </li></ul></ul><ul><ul><li>Week 4 </li></ul></ul><ul><ul><li>(Week 8) </li></ul></ul><ul><ul><li>Week 12 </li></ul></ul><ul><li>Free HCV testing and HAV/HBV vaccinations offered </li></ul>
    23. 25. Sample Knowledge Questions: SEP <ul><li>Which of the following can transmit HCV infection? (MC) </li></ul><ul><li>How often is hepatitis C passed on by sex? </li></ul><ul><ul><li>Never/rarely/frequently/DK </li></ul></ul><ul><li>Which of the following can you get vaccinated for? </li></ul><ul><li>Most people with hepatitis C don’t need treatment: T/F/DK </li></ul><ul><li>Most people with HCV get yellow jaundice: T/F/DK </li></ul><ul><li>Most people with hepatitis C will die from it: T/F/DK </li></ul>
    24. 26. Preliminary Results
    25. 27. Demographics 67% 59% Told HCV+ 72% 84% Tested for HCV 98% 97% Tested for HIV 42% 23% 1 0 care in ER 41% 30% Uninsured 26% 33% < High School 7 10 Latino (%) 50 41 Black (%) 42 42 White (%) 43 46 Age (x) 100/100 282/450 Enrollment SEP MMT
    26. 28. Demographics 19% 28% Tattoo in jail 51% 38% Prev STD 45% 13% > 3 sex partners <1yr 29% 34% Always condom 46% 58% Never condom 25% 17% Shared works <1yr 73% 51% Active EtOH 34% 33% HBV Vax 35% 33% HAV Vax SEP MMT
    27. 29. SEP Knowledge 33 21 30 41 40 n 29 30 23 ** ** ** ** ** P<0.001 for difference from usual care at all time points
    28. 30. MMT Knowledge Scores 84 85 52 68 47 73 53 43 n 36 ** P<0.001 for difference from usual care at all time points ** ** ** ** ** ** p=0.02
    29. 31. MMT Attitudes/Motivation 46 43 85 68 52 84 64 55 36 n p=0.02 p=0.01 p=0.19 * * * *
    30. 32. Transitioning Street-Recruited Heroin Users to HCV Treatment using Buprenorphine NIDA DA015629-01
    31. 33. Study Design Street-recruited Heroin Users Hepatitis C Viral Testing Active: 12-24 weeks buprenorphine Inactive: Ineligible HCV Treatment, n=50 Buprenorphine Maintenance Not Interested in HCV Treatment: 12 wk buprenorphine taper 24 week buprenorphine taper
    32. 34. Enrollment <ul><li>All screened = 415 </li></ul><ul><li>Eligible = 275 </li></ul><ul><ul><li>Ineligible = 140 (33%) </li></ul></ul><ul><ul><ul><li>Not viremic = 94 (23%) </li></ul></ul></ul><ul><ul><ul><li>On methadone = 29 (7%) </li></ul></ul></ul><ul><ul><ul><li>No opioid addiction = 17 (4%) </li></ul></ul></ul>
    33. 35. Relevance All Screened: n=415 n = 275 n = 188 n = 146
    34. 36. The study sample is representative NS 19.2% 23.4% 23.6% 23.9% Latino NS 41.8% 39.4% 40.0% 37.3% Black NS 33.6% 31.9% 32.0% 34.5% White NS 71.2% 73.9% 74.9% 70.4% Male NS 46 (24-64) 46 (24-64) 46 (24-69) 46 (20-69) Age 146 188 275 415 n P Value Start Study Meds Enroll Eligible Screened
    35. 37. *Significant for the difference between screened and eligible cohorts The study sample is representative NS 55.5 60.1 50.3 58.0 % Alcohol NS 77% 78% 76% 76% Genotype 1 NS 13.2 13.5 14.9 15.6 % Meth NS 50.0 48.6 50.6 47.5 % Cocaine <0.001* 54 55 53 46 ALT 25 25 25 24 Yr. exposed P Value Start Bupe Enroll Eligible Screened
    36. 38. Drug Use Week 0-12
    37. 39. Treatment Retention (n=146) 58% 45%
    38. 40. Interest in HCV Treatment (n=146) Early Bupe termination Chose HCV Tx Chose taper
    39. 41. HCV Treatment Outcomes <ul><li>Completed treatment, n=37 </li></ul><ul><li>Early termination, n=18 </li></ul><ul><ul><li>3 incarcerated </li></ul></ul><ul><ul><li>4 medical </li></ul></ul><ul><ul><li>10 FTS </li></ul></ul><ul><ul><li>1 side effects </li></ul></ul>
    40. 42. Outcomes by Genotype 37 10 26 21 13 7 32 11 20
    41. 43. Relevance to heroin users who initiate buprenorphine
    42. 44. Relevance to all eligible heroin users
    43. 45. OASIS Resources <ul><li>Providers: </li></ul><ul><ul><li>Hepatitis C University </li></ul></ul><ul><ul><ul><li>www.hcvu.org </li></ul></ul></ul><ul><li>Patients: </li></ul><ul><ul><li>HepC411 </li></ul></ul>

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