The Challenge of Addiction and Hepatitis C. Diana Sylvestre, MD University of CA, San Francisco OASIS

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1 The Challenge of Addiction and Hepatitis C Diana Sylvestre, MD University of CA, San Francisco OASIS

2 HCV Prevalence by Selected Groups United States Hemophilia Injection drug users HIV patients Hemodialysis STD clients Gen population adults Surgeons, PSWs* Pregnant women Military personnel 3.5% 2% 1% 0.3% 6% 10% 30% 79% 87% Average Percent Anti-HCV Positive * 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

3 Injecting Drug Use and HCV Transmission Highly efficient Contamination of drug paraphernalia, not just needles and syringes Rapidly acquired after initiation 30% prevalence after 3 years >50% prevalence after 5 years Four times more common than HIV Adapted from CDC Hepatitis Slide Kit.

4 Relative Importance of Risk Factors for Hepatitis C Remote (>15 yrs ago) Recent (<15 yrs ago) Transfusion Injection Drug Use Transfusion Unknown Injection Drug Use Other* Unknown Other* Sexual Sexual * Nosocomial, occupational, perinatal Adapted from CDC Hepatitis Slide Kit

5 Drug Users are heterogeneous Heroin Cocaine Methamphetamine Cannabis Polysubstance use Regular use Intermittent use Binge use Injection Intra-nasal Oral

6 The evidence for addiction as a brain disease Dopamine release in the Nucleus Accumbens is a common characteristic of virtually every drug of abuse. Frontal Cx Hippo N. Acc DMT AMG VTA LC Koob, Trends in Pharm Sci,,1992

7 Treatment options for depression Tricyclics (TCAs) Amitriptyline, imipramine, nortriptyline, etc. Monoamine oxidase inhibitors (MAOIs) Phenelzine, tranylcypromine, isocarboxazid, etc. Selective serotonin reuptake inhibitors (SSRIs) Fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, etc. Serotonin antagonists Trazodone, nefazodone Other agents Bupropion, venlafaxine, mirtazapine, reboxetine, etc.

8 Treatment options for addiction Alcohol Disulfiram, acamprosate, naltrexone Opiate Methadone, buprenorphine, naltrexone Stimulants?

9 Heroin-associated Mortality Hser, Y. I., et al. (2001) Arch Gen Psychiatry, 58,

10 Progression of Liver Fibrosis Among IDUs With Chronic HCV 119 prospectively followed IDUs Demographics 96% were African American 97% HCV genotype 1 27% HIV-infected Significant Median age fibrosis 42 years. at first biopsy: 90.7% After 4.2 years median followup 21% had progression of fibrosis Insignificant Fibrosis Significant Fibrosis Wilson LE, et al. Hepatology Apr;43(4): % 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 endstage liver disease.

11 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

12 The data As it exists.

13 HCV Treatment in Methadone Patients SVR Rates in Injection Drug Users in Detox (N = 50) Patients (%) Overall SVR 53 Relapsed and Returned to Treatment P = NS 24 n=15 n=25 Relapsed and Did Not Return to Treatment 40 n=10 Did Not Relapse Backmund M, et al. Hepatology. 2001;34:

14 Attendance predicts SVR 100 P < SVR, % n=38 n=12 >2/3 Appts <2/3 Appts Backmund M, et al. Hepatology. 2001;34:

15 Mauss, et al. (Hepatology, 2004) p=0.16 SVR % MMT Control 20 0 n=50 n=50 MMT Control

16 HCV Treatment in the Setting of Active Drug Use HCV Treatment Outcomes: Active IDUs vs Nonactive IDUs (N = 406) Active IDUs Patients (%) P = NS Noncompliance P = NS End of Treatment Response P = NS SVR Nonactive IDUs Robaeys G, et al. Eur J Gastroenterol Hepatol. 2005;18:

17 SVR Rate May Increase with Abstinence Degree of Drug Use and SVR (N = 76) Sustained Virologic Response (%) Regular P = Occasional 35 None P = < 6 mo 6 mo Substance Use Abstinence Duration Sylvestre DL, et al. J Subst Abuse Treatment. 2005;29:

18 Protective Immunity? Patients with ongoing or prior HCV infection may develop immunity that protects against further infection with HCV despite repeated exposure Dove L, Phung Y, Bzowej N, Kim M, Monto A, Wright TL. Viral evolution of hepatitis C in injection drug users. J Viral Hepat Nov;12(6): Grebely J, Conway B, Raffa JD, Lai C, Krajden M, Tyndall MW. Hepatitis C virus reinfection in injection drug users. Hepatology Nov;44(5): 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.

19 Current Studies at OASIS

20 A Brief HCV Prevention Education Intervention for Inand Out-of- Treatment Drug Users CDC U50/CCU923257

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23 Protocol Two test populations, two video curricula: Out of treatment drug users at syringe exchange, n=100 Brief, 7-minute peer-based prevention education video In-treatment drug users enrolled in methadone maintenance, n= minute peer based education video Two viewing formats: single session vs. 4 session

24 Protocol Demographic/risk behavior questionnaire Randomization: Usual care vs. video intervention SEP 1:1 MMT 1:1:1 (1 usual care: 1 single session: 1 4-part viewing) KAM test (Knowledge/Attitudes/Motivations) Baseline Immediate post video Week 4 (Week 8) Week 12 Free HCV testing and HAV/HBV vaccinations offered

25 Sample Knowledge Questions: SEP Which of the following can transmit HCV infection? (MC) How often is hepatitis C passed on by sex? Never/rarely/frequently/DK Which of the following can you get vaccinated for? Most people with hepatitis C don t need treatment: T/F/DK Most people with HCV get yellow jaundice: T/F/DK Most people with hepatitis C will die from it: T/F/DK

26 Preliminary Results

27 Demographics MMT SEP Enrollment 282/ /100 Age (x) White (%) Black (%) Latino (%) 10 7 < High School 33% 26% Uninsured 30% 41% 1 0 care in ER 23% 42% Tested for HIV 97% 98% Tested for HCV 84% 72% Told HCV+ 59% 67%

28 Demographics MMT SEP HAV Vax 33% 35% HBV Vax 33% 34% Active EtOH 51% 73% Shared works <1yr 17% 25% Never condom 58% 46% Always condom 34% 29% >3 sex partners <1yr 13% 45% Prev STD 38% 51% Tattoo in jail 28% 19%

29 SEP Knowledge % Improvement ** ** ** P<0.001 for difference from usual care at all time points ** ** n Post Video Wk 4 Wk 8 Wk 12 Usual Video

30 MMT Knowledge Scores ** p=0.02 ** P<0.001 for difference from usual care at all time points % Improvement ** ** ** ** ** Usual Single 4-part 10 0 n Post Video Wk 4 Wk 12

31 MMT Attitudes/Motivation n Post Video p=0.02 * * Wk 4 p=0.01 * * part Single Usual Wk p= Change in Score

32 Transitioning Street- Recruited Heroin Users to HCV Treatment using Buprenorphine NIDA DA

33 Study Design Street-recruited Heroin Users Hepatitis C Viral Testing Inactive: Ineligible Not Interested in HCV Treatment: 12 wk buprenorphine taper Active: weeks buprenorphine 24 week buprenorphine taper HCV Treatment, n=50 Buprenorphine Maintenance

34 Enrollment All screened = 415 Eligible = 275 Ineligible = 140 (33%) Not viremic = 94 (23%) On methadone = 29 (7%) No opioid addiction = 17 (4%)

35 Relevance All Screened: n=415 % Patients n = 275 n = 188 n = 146 Eligible Enrolled Start Bupe

36 The study sample is representative Screened Eligible Enroll Start Study Meds n P Value Age NS (20-69) (24-69) (24-64) (24-64) Male 70.4% 74.9% 73.9% 71.2% NS White 34.5% 32.0% 31.9% 33.6% NS Black 37.3% 40.0% 39.4% 41.8% NS Latino 23.9% 23.6% 23.4% 19.2% NS

37 The study sample is representative Screened Eligible Enroll Start Bupe P Value Yr. exposed ALT <0.001* % Cocaine NS % Meth NS % Alcohol NS Genotype 1 76% 76% 78% 77% NS *Significant for the difference between screened and eligible cohorts

38 Drug Use Week 0-12 % UA Op Coc Meth MJ ` Baseline Week 4 Week 8 Week 12

39 Treatment Retention (n=146) 150 Number of Patients % % Weeks on Buprenorphine

40 Interest in HCV Treatment (n=146) 10 Chose HCV Tx Early Bupe termination

41 HCV Treatment Outcomes Completed treatment, n=37 Early termination, n=18 3 incarcerated 4 medical 10 FTS 1 side effects

42 Outcomes by Genotype % All Pts Geno 1 Geno non Completed ETR SVR

43 Relevance to heroin users who initiate buprenorphine Percent Start HCV Tx Complete HCV Tx SVR

44 Relevance to all eligible heroin users Percent Initiate Bupe Start HCV Tx Complete HCV Tx SVR

45 OASIS Resources Providers: Hepatitis C University Patients: HepC411