HCV in Addicted Patients:HCV in Addicted Patients:Overcoming the Barriers to Overcoming the Barriers to Education, Treatment, and Education, Treatment, and

OutcomesOutcomes

Diana L. Sylvestre, MDDiana L. Sylvestre, MDExecutive Director, OASISExecutive Director, OASIS

Presented by: Amy Smith, PA-CPresented by: Amy Smith, PA-C

OASISOASIS

Organization to Organization to Achieve Solutions in Achieve Solutions in

Substance-AbuseSubstance-Abuse

Our situationOur situation

• Poverty, high rates of drug usePoverty, high rates of drug use– Heroin, crack cocaine, Heroin, crack cocaine,

methamphetaminemethamphetamine

• Low rates of health insuranceLow rates of health insurance– Limited access to medical careLimited access to medical care– Limited access to drug treatmentLimited access to drug treatment

• Limited access to healthcareLimited access to healthcare

Our Mission:Our Mission:

Provide high quality Provide high quality medical care to drug users medical care to drug users

(or whoever shows up)(or whoever shows up)

A Small Community A Small Community ClinicClinic

• One doctor One doctor • One physician assistant (Me)One physician assistant (Me)• 3 peer educators3 peer educators• No nurses, social workers, or case No nurses, social workers, or case

managersmanagers• A lot of willing volunteersA lot of willing volunteers

A Small Community Clinic A Small Community Clinic with an Evidence-based with an Evidence-based

ApproachApproach• Addiction is a medical illnessAddiction is a medical illness• Treatments are limited and relapse Treatments are limited and relapse

is characteristicis characteristic• Perfection is an unrealistic Perfection is an unrealistic

expectationexpectation

Treatment options Treatment options for hypertensionfor hypertension

• DiureticsDiuretics– HCTZ, spironolactone, furosemide, amiloride, HCTZ, spironolactone, furosemide, amiloride,

triamterene, etc.triamterene, etc.• ACE InhibitorsACE Inhibitors

– Benazepril, captopril, enalapril, fosinopril, Benazepril, captopril, enalapril, fosinopril, lisinopril, quinapril, ramipril, etc.lisinopril, quinapril, ramipril, etc.

• Beta BlockersBeta Blockers– Propranolol, atenolol, metoprolol, pindolol, labetolo, Propranolol, atenolol, metoprolol, pindolol, labetolo,

carvedilol, timolol, sotalol, nadolol, etccarvedilol, timolol, sotalol, nadolol, etc• ARBsARBs

– Irbesartan, losartan, candesartan, valsartan, Irbesartan, losartan, candesartan, valsartan, olmesartan, telmisartan, etc. olmesartan, telmisartan, etc.

• Calcium Channel Blockers Calcium Channel Blockers – Verapamil, diltiazem, nifedipine, nicardipine, Verapamil, diltiazem, nifedipine, nicardipine,

amlodipine, felodipine, etc.amlodipine, felodipine, etc.

Treatment options Treatment options for diabetesfor diabetes

• InsulinsInsulins– Aspart, Glargine, Lispro, glulisineAspart, Glargine, Lispro, glulisine

• SulfonylureasSulfonylureas– Chlorpropamide, tolbutamide, tolazamideChlorpropamide, tolbutamide, tolazamide– Glipizide, glyburideGlipizide, glyburide– GlimeprirideGlimepriride

• BiguanidesBiguanides– MetforminMetformin

• Alpha-glucosidase inhibitorsAlpha-glucosidase inhibitors– Acarbose, miglitolAcarbose, miglitol

• GlitazonesGlitazones– Pioglitazone, rosiglitazonePioglitazone, rosiglitazone

• Megiltinides Megiltinides – RepaglinideRepaglinide

Treatment options Treatment options for depressionfor depression

• Tricyclics (TCAs)Tricyclics (TCAs)– Amitriptyline, imipramine, nortriptyline, etc.Amitriptyline, imipramine, nortriptyline, etc.

• Monoamine oxidase inhibitors (MAOIs)Monoamine oxidase inhibitors (MAOIs)– Phenelzine, tranylcypromine, isocarboxazid, Phenelzine, tranylcypromine, isocarboxazid,

etc.etc.

• Selective serotonin reuptake inhibitors (SSRIs)Selective serotonin reuptake inhibitors (SSRIs)– Fluoxetine, sertraline, paroxetine, Fluoxetine, sertraline, paroxetine,

fluvoxamine, citalopram, etc.fluvoxamine, citalopram, etc.

• Serotonin antagonistsSerotonin antagonists– Trazodone, nefazodone Trazodone, nefazodone

• Other agents Other agents – Bupropion, venlafaxine, mirtazapine, Bupropion, venlafaxine, mirtazapine,

reboxetine, etc.reboxetine, etc.

Treatment options for Treatment options for addictionaddiction

• AlcoholAlcohol– Disulfiram, acamprosate, naltrexoneDisulfiram, acamprosate, naltrexone

• OpiateOpiate– Methadone, buprenorphine, Methadone, buprenorphine,

naltrexonenaltrexone• StimulantsStimulants

– ??

Addiction is not a single Addiction is not a single syndrome:syndrome:

Cannabis

Methamphetamine

CocaineHeroin

Regular use

Binge use

Alcohol

Polysubstance use

Intermittent use

The evidence for addiction The evidence for addiction as a brain diseaseas a brain disease

Dopamine release in the Nucleus Dopamine release in the Nucleus Accumbens is a common Accumbens is a common characteristic of virtually every drug of characteristic of virtually every drug of abuse.abuse.

Koob, Trends in Pharm Sci, ,1992

DMT VTA

LC

Frontal Cx

N. Acc

Hippo

AMG

It quickly became It quickly became apparent that our apparent that our

little clinic had a big little clinic had a big problem:problem:

HEPATITIS CHEPATITIS C

Hepatitis C in OaklandHepatitis C in Oakland

• 96% of long-term injectors96% of long-term injectors• Limited access to drug Limited access to drug

treatmenttreatment• Syringe exchange available Syringe exchange available

on a limited basison a limited basis

How we came to How we came to treat hepatitis C:treat hepatitis C:

No one else would No one else would do it.do it.

Relative Importance of Relative Importance of Risk Factors for Risk Factors for

Hepatitis CHepatitis C Remote (>15 yrs ago) Recent (<15 yrs ago)

Transfusion

Sexual

Other*

Unknown

TransfusionInjection Drug Use

Unknown

Other*Sexual

Injection Drug Use

* Nosocomial, occupational, perinatalAdapted from CDC Hepatitis Slide Kit http://www.cdc.gov/ncidod/diseases/hepatitis/slideset

Natural history: Natural history: addictionaddiction

Hser, Y. I., et al. (2001) Arch Gen Psychiatry, 58, 503-8.

No one else would No one else would do it.do it.

We decided to try.We decided to try.

Hepatitis C Hepatitis C Treatment in Drug Treatment in Drug

UsersUsers

No one wants to No one wants to treat drug users for treat drug users for

hepatitis C.hepatitis C.

Why?Why?

Barriers: Barriers: perceived vs. realperceived vs. real

• Adherence is badAdherence is bad• Reinfection Reinfection • Interferon can exacerbate Interferon can exacerbate

psychiatric symptomspsychiatric symptoms• Interferon is an injectable Interferon is an injectable

medication and may increase the medication and may increase the risk for relapserisk for relapse

Most HCV treatment Most HCV treatment barriers are perceived barriers are perceived

or relative.or relative.

The real barrier is The real barrier is prejudiceprejudice..

Bridging Active Heroin Bridging Active Heroin Users to HCV Users to HCV

Treatment with Treatment with BuprenorphineBuprenorphine

1 R01 DA015629-01

HypothesisHypothesis

• Active, street-recruited heroin users Active, street-recruited heroin users can be safely and successfully can be safely and successfully treated for hepatitis C after 12-24 treated for hepatitis C after 12-24 weeks of buprenorphine weeks of buprenorphine stabilization.stabilization.

Study DesignStudy DesignStreet-recruited

Heroin Users

Hepatitis C Viral Testing

Active: 12-24 weeks buprenorphine

Inactive: Ineligible

HCV Treatment, n=50Buprenorphine Maintenance

Not Interested in HCV Treatment: 12 wk buprenorphine taper

24 week buprenorphine taper

EnrollmentEnrollment

• All screened = 415All screened = 415

• Eligible = 275Eligible = 275– Ineligible = 140 (33%)Ineligible = 140 (33%)

• Not viremic = 94 (23%)Not viremic = 94 (23%)• On methadone = 29 (7%)On methadone = 29 (7%)• No opioid addiction = 17 (4%)No opioid addiction = 17 (4%)

RelevanceRelevanceAll Screened: n=415All Screened: n=415

68

53

0

10

20

30

40

50

60

70

80

90

100

Eligible Enrolled Start Bupe

% P

atie

nts

n = 275 n = 188 n = 146

ScreenedScreened EligibleEligible EnrollEnroll Start Start Study Study MedsMeds

P ValueP Value

nn 415415 275275 188188 146146AgeAge 46 46

(20-(20-69)69)

46 46

(24-(24-69)69)

46 46

(24-(24-64)64)

46 46

(24-(24-64)64)

NSNS

MaleMale 70.4%70.4% 74.9%74.9% 73.9%73.9% 71.2%71.2% NSNSWhitWhitee

34.5%34.5% 32.0%32.0% 31.9%31.9% 33.6%33.6% NSNS

BlackBlack 37.3%37.3% 40.0%40.0% 39.4%39.4% 41.8%41.8% NSNSLatinLatinoo

23.9%23.9% 23.6%23.6% 23.4%23.4% 19.2%19.2% NSNS

The study sample is The study sample is representativerepresentative

ScreenedScreened EligibleEligible EnrollEnroll Start Start BupeBupe

P ValueP Value

Yr. Yr. exposedexposed

2424 2525 2525 2525

ALTALT 46 46 5353 5555 5454 <0.001<0.001**

% Cocaine% Cocaine 47.547.5 50.650.6 48.648.6 50.050.0 NSNS% Meth% Meth 15.615.6 14.914.9 13.513.5 13.213.2 NSNS% Alcohol% Alcohol 58.058.0 50.350.3 60.160.1 55.555.5 NSNSGenotype Genotype 11

76%76% 76%76% 78%78% 77%77% NSNS*Significant for the difference between screened and eligible cohorts

The study sample is The study sample is representativerepresentative

Other Other CharacteristicsCharacteristics

• 33% homeless33% homeless• Median education < high schoolMedian education < high school• Median monthly income ~$550 USDMedian monthly income ~$550 USD• 40% on probation or parole, median 40% on probation or parole, median

weeks of prior incarceration = 156weeks of prior incarceration = 156• 64% with history of “serious depression”, 64% with history of “serious depression”,

75% with history of “serious anxiety,” 75% with history of “serious anxiety,” 22% had prior suicide attempt. 14% had 22% had prior suicide attempt. 14% had been prescribed a psychiatric medication.been prescribed a psychiatric medication.

• Median number of prior treatment Median number of prior treatment attempts = 7attempts = 7

Criteria for initiating Criteria for initiating HCV treatmentHCV treatment

– Active HCVActive HCV– InterestedInterested– Attendance of >75% of weekly Attendance of >75% of weekly

education sessionseducation sessions

Drug Use Week 0-12Drug Use Week 0-12

0

1020

30

4050

60

70

8090

100

Op Coc Meth MJ

% U

A +

Baseline

Week 4

Week 8

Week 12

`

Treatment Retention Treatment Retention (n=146)(n=146)

108

9383

76 7266

-10

10

30

50

70

90

110

130

150

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Weeks on Buprenorphine

Num

ber o

f Pat

ient

s

58%45%

Interest in HCV Interest in HCV Treatment (n=146)Treatment (n=146)

8155

10

Early Bupe termination

Chose HCV Tx

Chose taper

Drug Use and HCV Drug Use and HCV Treatment RetentionTreatment Retention

0102030405060708090

100

% C

ompl

etin

g H

CV

Tx

None

Any hard drugs

Drug Use and HCV Drug Use and HCV Treatment RetentionTreatment Retention

0

10

20

30

40

50

60

70

80

90

100

% C

om

ple

tin

g H

CV

Tx

None

Any hard drugs

MJ+

Drug Use and HCV Drug Use and HCV Treatment RetentionTreatment Retention

0102030405060708090

100

% C

ompl

etin

g H

CV

Tx

None

Stim+

Any hard drugs

Drug Use and HCV Drug Use and HCV Treatment RetentionTreatment Retention

0102030405060708090

100

% C

om

ple

tin

g H

CV

Tx

None

Any hard drugs

Her+

Drug Use and HCV Drug Use and HCV Treatment RetentionTreatment Retention

0102030405060708090

100

% C

om

ple

ting

HC

V T

x

None

Stim+

Her+

HCV Treatment HCV Treatment OutcomesOutcomes

• Completed treatment, n=38Completed treatment, n=38• Early termination, n=18Early termination, n=18

– 3 incarcerated3 incarcerated– 4 medical4 medical– 10 FTS10 FTS– 1 side effects1 side effects

Outcomes by GenotypeOutcomes by Genotype

6859

40

62

48

32

91100

64

0

10

20

30

40

50

60

70

80

90

100

Completed ETR SVR

%

All Pts

Geno 1

Geno non-1

37 1026 21 13 732 1120