Treatment of Hepatitis C in People Who

Inject Drugs (PWIDs)

Andrew Seaman, MD

OHA P&T Meeting

January, 2017

Conflicts of interest

Receive <8% of my salary from an investigator initiated, Merck

funded trial (makers of elbasvir/grazoprevir)

I am highly influenced by the opinions, life experience, and

knowledge my patients bring to the table (many of whom inject

drugs)

Objectives

Review of published and some unpublished data on PWIDs from

colleagues in New York, Australia, Europe

Brief review of the Old Town Clinic / Outside In / OHSU pilot trial for

HCV treatment in People Who Inject Drugs

Alcohol use does not affect SVR12

Tsui et al. Drug Alcohol Depend. 2016 Dec 1;169:101-109.

C-EDGE CO-STAR Trial

Multicenter-RCT tx w/ Elb-Graz with 301 PWIDs

Patients with GT 1, 4, or 6 HCV on either methadone (81%) or buprenorphine (19%) for

comorbid opioid use disorder

Randomized 2:1 to immediate treatment group vs delayed treatment group (12wks

placebo + 4 weeks de-randomization + 12 weeks treatment)

Primary outcome SVR 12 assuming re-infection as cure

Intention-to-treat analysis

Dore et al. Ann Intern Med. 2016;165:625-634

C-EDGE CO-STAR Trial

**2 year f/u re-infection data

2.3/100pyrs

Dore et al. Ann Intern Med. 2016;165:625-634

Imm. Treat. Group

(n=201)

SVR 12 SVR 24

Assuming Re-

infections are

Responses

94% (89.8-96.9) 85% (78.8-89)

*2/201 additional

relapses

Assuming Re-

infections =

Treatment Failure

91.5% (CI 86.8-

95%)

87%

Probable

Reinfection

5/201 5/201

Lost to Follow Up 3 15

Adherence >95% ~95% 95%

SIMPLIFY trial (pre-publication)

Multicenter, international RCT with recent (<6mo) PWIDs

103 participants w/ GT 1-6 HCV

Treated w/ Sof/Vel x 12 weeks

Primary endpoint SVR12, secondary Adherence > 90%

Results

70% injecting in last month

57% receiving opioid substitution therapy

End Treatment Response – 94% (NO confirmed VL failures – 6% loss to f/u)

SVR12 and Adherence data pending

Reinfection data pending (f/u 3 years)

Grebely et al. Hepatology. 2017Volume 66, Issue 1, Supplement, Page S513

Intensive management of HCV tx in

PWIDs: Montefiore trial

PREVAIL study: Unpublished data from INHSU. LINK to slides.

OTC – OI – OHSU Pilot Study

Prospective, non-randomized real world clinical trial using elb/graz

to treat people who inject drugs with GT 1 or 4 HCV and an APRI

<0.7 who:

Arm 1: engage with Medication Assisted Therapy (Methadone/Bupe),

n=25, Old Town Clinic

Arm 2: are actively using and engage with needle exchange program,

n=25, Outside In

Arm 3: matched cohort in OHSU hepatology clinic, n=50

Endpoints

Primary

SVR 12 and 48

Secondary

Primary Tx failure (+RNA 24wks)

Secondary Tx Failure (+RNA 60wks)

Adherence

Discontinuation rate

NS5a resistance

Substance use relapse

OHSU-OTC-OI Study Progress:

Enrollment

Old Town Clinic / MAT:

25/25 enrolled

Adherence greater than 95% (All patients completed by Jan, SVR data

by April 1)

Outside In

14/25 enrolled

Adherence good except 2/10 lost-to f/u (? Sampling error)

OHSU

Pending

Limitations

Power

Powered to detect a difference of 20% in primary endpoint; this is not

clinically ideal

Group Disparities

Comparing prospective trial w/ very specific inclusion criteria to chart

biopsy based cohort

Difference in un-measurables between people in MAT program and

needle exchange (and university setting)

Differences in pre-screening process

Old Town Clinic Treatment Program

Multidisciplinary

Medical director + two providers

HCV coordinator

Clinical pharmacist

CADC

Weekly committee meetings

Decision made on need for treatment candidacy, Substance Used

Disorder support, adherence support

Drug, labs ordered and PA process started by coordinator

First, last, and SVR visit by provider, remainder by pharmacist

We treat… everyone

Treatment candidacy

Made 2/3 last appointments or subjective adherence measure

(whichever lower barrier)

Desires treatment

Meets their insurance eligibility criteria*

*We consider any SUDs support as treatment and have had great success

with insurers

Our capacity

A total of 60 patients have initiated treatment in the last 9.5 months

(24 study/36 non-study).

We expect to treat many more in 2018.

0

2

4

6

8

10

12

14

Mar Apr May Jun Jul Aug Sep Oct Nov Dec

HCV Treatment Initiation 2017

Program Study Both Linear (Program)

36

1421

1

24

18 6

0

10

20

30

40

50

60

70

Started Tx (60) Finished Tx (32) Active Tx (27) Discontinued (1)

OTC HCV Treatment Snapshot

Program Study

Adherence

Adherence has been near perfect in almost all cases.

The 4 exceptions are: #1 ‘completed’ 1 month interruption, #2

‘discontinued’ completed 8 weeks, #3 ‘active’ 15 day interruption &

#4 ‘active’ 24 day interruption.

93.3%

6.7%

Adherence - Not active

Great Adherence (28) Adherence Issues (2)

Treatment efficacy

Everyone that completed a SVR12 viral load has been

undetectable.

7

4 4

8

8 8

0

2

4

6

8

10

12

14

16

Due for lab (15) Results received (12) SVR12 achieved (12)

HCV SVR12

Program Study

Treatment as prevention depends

on treating PWIDs

Despite reinfection risk, not treating leads to a greater public health

risk

If we are not treating a patient population with at least some re-

infection risk we are not treating the population that transmits this

virus

Multiple models suggest that we must treat PWIDs if we are to

successfully address the HCV epidemic9,10

In Summary: We can and must

treat hep C in PWIDs

There is no evidence of different hepatitis C treatment outcomes

among people with or without substance use disorders

The WHO and others recommend we prioritize rather than restrict

treatment in PWIDs

Mathematical models and common sense suggest we cannot treat

this epidemic unless we treat the people transmitting the virus

Where is the rational for denying people with substance use

disorders?? The rational for “6 months sobriety?”

(Why not deny diabetics? People with metabolic syndrome?

Tobaccoism?)

HCVguidelines.org

Questions?

References

1. Centers for Disease Control and Prevention. Viral Hepatitis Surveillance—United States, 2014. https://www.cdc.gov/hepatitis/statistics/2014surveillance/commentary.htm#Ref30

2. E Paintsil, H He, C Peters, and others. Survival of HCV in Syringes: Implication for HCV Transmission among Injection Drug Users. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 168.

3. Platt L, Minozzi S, Reed J, Vickerman P, Hagan H, French C, Jordan A, Degenhardt L, Hope V, Hutchinson S, Maher L, Palmateer N, Taylor A, Bruneau J, Hickman M. Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD012021.

4. Grebely et al. Efficacy and safety of sofosbuvir/velpatasvir in people with chronic hepatitis C virus infection and recent injecting drug use: the SIMPLIFY study. 2017Volume 66, Issue 1, Supplement, Page S513

5. Read et al. Delivering direct acting antiviral therapy for hepatitis C to highly marginalised and current drug injecting populations in a targeted primary health care setting. International Journal of Drug Policy 47 (2017) 209–215.

6. Tsui et al. Drug Alcohol Depend. 2016 Dec 1;169:101-109.

7. Dore et al. Ann Intern Med. 2016;165:625-634.

8. Pineda et al. Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C. Infection. November 2015Volume 71, Issue 5, Pages 571–577.

References Continued

9. Martin et al.

Hepatitis C virus treatment for prevention among people who inject

drugs: Modeling treatmentscale-up in the age of direct-

acting antivirals. Hepatology. 2013 Nov;58(5):1598-609.

10. Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, Vickerman

P.Combination interventions to prevent HCV transmission among

people who inject drugs: modeling the impact of antiviral

treatment, needle and syringe programs, and opiate substitution

therapy. Clin Infect Dis. 2013;57(Suppl 2):S39-S45.

11. Durier N, Nguyen C, White LJ. Treatment of hepatitis C as

prevention: a modeling case study in Vietnam. PLoS One.

2012;7(4):e34548.