Transitioning street-

recruited heroin users to

HCV treatment using

buprenorphineNIDA DA015629-01

Diana Sylvestre, MD

University of CA, San Francisco

OASIS (Organization to Achieve Solutions in Substance-Abuse)

NIDA DA015629-01

HCV and addiction:

an insurmountable problem?

• 70% of IDUs in US exposed

– Easily transmitted

• Treatment can be toxic • Treatment can be toxic

– Often “contraindicated”

• Medical

• Psychiatric

• Reinfection?

A different perspective

Addiction HCV

Pharmacologic

therapy

Yes (+/-) Yes

therapy

Treatment

duration

Indefinite 24-48 weeks

Cure No Yes

Natural history: addictionNatural history: addictionNatural history: addictionNatural history: addiction

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

Natural History of HCV

Infection

Resolved

15% to 40%

Acute HCV

Chronic HCV

60% to 85%

Stable

85% to 90%

HCC,liver failure

25% (2% to 4%)Slowly

progressive

75%

Cirrhosis

10% to 15%

NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed April 10, 2007.

How should we

intervene?

Priority

• Addiction?

• HCV?

Priority

• Diabetes?

• High blood pressure?

Priority

• Diabetes AND high blood pressure

• Addiction AND hepatitis C

HCV Treatment HCV Treatment HCV Treatment HCV Treatment

Recommendations: 2002Recommendations: 2002Recommendations: 2002Recommendations: 2002

“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 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

HCV Treatment in

Methadone Patients

P = NS80

100

Pa

tie

nts

(%

)

SVR Rates in Injection Drug Users on Methadone Detox (N = 50)

36

53

24

40

Overall SVR Relapsed and

Returned toTreatment

Relapsed and Did Not

Return to Treatment

Did NotRelapse

Backmund M, et al. Hepatology. 2001;34:188-193.

0

20

40

60

80

Pa

tie

nts

(%

)

n=10n=15 n=25

HCV Treatment Outcomes in

Methadone Patients

38P = .16

P = .0140

Patients on methadone maintenance (n=50) Controls (n=50)

2528

21

EOT SVR

P = .16

Response OutcomesMauss S, et al. Hepatology. 2004;40:120-124.

Pa

tie

nts

(%

)

10

20

30

0

HCV Treatment Outcomes in

Methadone Patients

30

35

30

40

Su

sta

ine

d V

iro

log

ic R

es

po

ns

e (

%)

Degree of Drug Use and SVR (N = 76)

P = .18P = .09

≥ 6 mo< 6 moNoneOccasionalRegular

Abstinence DurationSubstance Use

2221

0

Sylvestre DL, et al. J Subst Abuse Treatment. 2005;29:159-165.

10

20

30

Su

sta

ine

d V

iro

log

ic R

es

po

ns

e (

%)

0

HCV Treatment in the

Setting of Active Drug Use

Active IDUs

Nonactive IDUs

HCV Treatment Outcomes: Active IDUs vs Nonactive IDUs (N = 406)

80

100P = NS

P = NS

0

48

31

7.6

6150

Noncompliance End of TreatmentResponse

SVR

Pa

tie

nts

(%

)

P = NS

Robaeys G, et al. Eur J Gastroenterol Hepatol. 2005;18:159-166.

0

20

40

60

80P = NS

P = NS

Approaches to

Intervention:

O.A.S.I.S. Study

Our setting

Our situation

• Poverty, high rates of drug use

– Heroin, crack cocaine, methamphetamine

• Very high HCV seroprevalence

– ~95% of IDUs– ~95% of IDUs

• Low rates of health insurance

– Limited access to medical care

– Limited access to drug treatment

• Syringe exchange is disliked but tolerated

– (usually)

Hypothesis

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

Study DesignStudy DesignStudy DesignStudy Design

Heroin Users at Syringe Exchange

Hepatitis C Viral Testing

Inactive: Ineligible

Active: 12-24 weeks buprenorphine

HCV Treatment, n=50Buprenorphine Maintenance

Not Interested in HCV Treatment: 12 wk buprenorphine taper

24 week buprenorphine taper

Criteria for initiating

HCV treatment

–Active HCV–Active HCV

–Interested

–Attendance of >75% of

weekly education sessions

Enrollment

• All screened = 415

• Eligible = 275

– Ineligible = 140 (33%)– Ineligible = 140 (33%)

• Not viremic = 94 (23%)

• On methadone = 29 (7%)

• No opioid addiction = 17 (4%)

RelevanceRelevanceRelevanceRelevanceAll Screened: n=415All Screened: n=415All Screened: n=415All Screened: n=415

6870

80

90

100

53

0

10

20

30

40

50

60

70

Eligible Enrolled Start Bupe

% P

ati

en

ts

n = 275 n = 188 n = 146

Screened Eligible Enroll Start Study Meds

P Value

n 415 275 188 146Age 46 46 46 46 NS

The study sample is

representative

Age 46

(20-69)

46

(24-69)

46

(24-64)

46

(24-64)

NS

Male 70.4% 74.9% 73.9% 71.2% NSWhite 34.5% 32.0% 31.9% 33.6% NSBlack 37.3% 40.0% 39.4% 41.8% NSLatino 23.9% 23.6% 23.4% 19.2% NS

Screened Eligible Enroll Start Bupe

P Value

Yr. exposed 24 25 25 25

ALT 46 53 55 54 <0.001*

The study sample is

representative

ALT 46 53 55 54 <0.001*

% Cocaine 47.5 50.6 48.6 50.0 NS

% Methamp 15.6 14.9 13.5 13.2 NS

% Alcohol 58.0 50.3 60.1 55.5 NS

*Significant for the difference between screened and eligible cohorts

Drug Use Week 0-12

70

80

90

100

Baseline

0

10

20

30

40

50

60

Op Coc MA MJ

% U

A +

Baseline

Week 4

Week 8

Week 12

`

Treatment Retention Treatment Retention Treatment Retention Treatment Retention

(n=146)(n=146)(n=146)(n=146)

108

9383

110

130

150

Nu

mb

er

of

Pa

tie

nts

58%45%

8376 72

66

-10

10

30

50

70

90

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

Nu

mb

er

of

Pa

tie

nts

Interest in HCV

Treatment

Interest in HCV

Treatment

10

8155

Early Bupe termination

Chose HCV Tx

HCV Treatment

Outcomes

• Completed treatment, n=37

• Early termination, n=18– 3 incarcerated

– 4 medical

– 10 failed to show

– 1 side effects

HCV Treatment

Outcomes

67

5860

70

80

33

40

0

10

20

30

40

50

Early Term Completed Tx ETR SVR

Pe

rce

nt

n=18 n=37 n=32 n=22

Outcomes by Genotype

68

5962

91100

64

60

70

80

90

100

All Pts

4048

32

0

10

20

30

40

50

60

Completed ETR SVR

%

All Pts

Geno 1

Geno non-1

37 1026 22 14 832 1120

Relevance to heroin users

who initiate buprenorphine

60

70

80

90

100

38

26

16

0

10

20

30

40

50

60

Start HCV Tx Complete HCV Tx SVR

Pe

rce

nt

Relevance to all eligible

heroin users

5360

70

80

90

100

Pe

rce

nt 53

2014

8

0

10

20

30

40

50

60

Initiate Bupe Start HCV Tx Complete HCV

Tx

SVR

Pe

rce

nt

Current Questions

• Can we predict who will successfully complete HCV treatment?

• Can we predict who will initiate HCV treatment?treatment?

• How can we maximize engagement and outcomes?

Acknowledgments

• NIDA

• OASIS Staff

– Christopher McNeil

– Laphyne Barrett– Laphyne Barrett

• East Bay Community Recovery Project