The Syndemicof Hepatitis C in Opioid Use Disorder

The Syndemic of Hepatitis C in Opioid Use Disorder

MACS WebinarApril 12, 2021

Sarah Kattakuzhy, MDAssistant Professor

Institute of Human Virology at the University of Maryland School of Medicine

1-855-337-MACS (6227) • www.marylandMACS.org

Provides support to prescribers and their practices in addressing the needs of their patients with substance use disorders and chronic pain management.

All Services are FREE

• Phone consultation for clinical questions

• Education and training opportunities related to substance use disorders and chronic pain management

• Assistance with addiction and behavioral health resources and referrals

• Technical assistance to practices implementing or expanding office-based addiction treatment services

• MACS TeleECHO™ Clinics: collaborative medical education through didactic presentations and case-based learning

Maryland Addiction Consultation Service (MACS)

Disclosures

• Dr. Kattakuzhy was the PI on a grant for investigator-sponsored research from Gilead Sciences paid to the institution (2016)

Why Syndemic?

Epidemic of Hepatitis C

Syndemic of Hepatitis C and

Opioid Use Disorder

What Is A Syndemic?

“A syndemic, or synergistic epidemic, is more than a convenient portmanteau or a synonym for comorbidity. The hallmark of a syndemic is the presence of two or more disease states that adversely interact with each other, negatively affecting the mutual course of each disease trajectory, enhancing vulnerability, and which are made more

deleterious by experienced inequities.”

Lancet Editorial, 2017

Outline

Viral Characteristics and Epidemiology

Challenges and Strategies

Diagnosis, Treatment, and Monitoring

Viral Characteristics and Epidemiology

Kaito M, Watanabe S, Tsukiyama-Koham K, et al. Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol. 1994;75:1755-1760.)

HCV Viral Features: Structure

• RNA virus–Positive single stranded–Family Flaviviridae–Genus Hepacivirus

• In vivo replication in hepatocytes–Highly error prone, trillions of virions/day

HCV Viral Features: Survival

1. Paintsil E, et al. J Infect Dis. 2010;202(7):984-990; 2. Doerrbecker J, et al. J Infect Dis. 2011;204(12):1830-1838; 3. Thibault V, et al. J Infect Dis. 2011;204(12):1839-1842; 4. Doerrbecker J, et al. J Infect Dis. 2013;207(2):281-287; 5. Paintsil E, et al. J Infect Dis. 2014; 209(8):1205-1211; 5. Zibbell J. Hepatitis C Prevention Opportunities Among PWID. April 28, 2015. Presentation. https://www.hhs.gov/sites/default/files/hcv-in-pwid-webinar.pdf. 6. Image source: http://qdsyringesystems.com

Survival on Inanimate Objects1−5

Days

Survival at High Temperature1−5

An HCV-contaminated solution needs to be heated for 90

seconds at 144°F for the virus to be at undetectable levels.

Transmission via Contact With Contaminated

Needle/Syringe6

HIGHDead-Space

Syringe (DSS)

DETACHABLENeedle With

Low DSS

FIXEDNeedle With

Low DSS

Use and sharing of high DSSs isassociated with increased risk of

HCV infection.

1

3

21

21

64

0 20 40 60 80

Filter

Foil

Surface

Water container

Syringe

HCV Viral Features: Genotype

Messina, Hepatology, 2015

HCV Transmission

6015

10

4

10

Injection Drug UseSexualTransfusion before 1985OccupationalUnknown

https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm.

World Health Organization. Global hepatitis report 2017

HCV Epidemiology: Global

Prevalence: 71 million

Incidence: 1.75 million/year

HCV Epidemiology: US

3.7 million people HCV Ab+

Hep Vu

Incidence of Acute Hepatitis C by Year in the United States, 2006-2016

https://www.cdc.gov/hepatitis/statistics/2016surveillance/index.htm

Changing Epidemiology of HCV in the US

Male

Female

Mostly baby boomers

New

ly R

epor

ted

HC

V C

ases

, %

5

0 10 20 30 40

Age, Years

4

3

2

1

050 60 70 80 90 100

2007 (N = 41,037)

New

ly R

epor

ted

HC

V C

ases

, %

5

0 10 20 30 40

Age, Years

4

3

2

1

050 60 70 80 90 100

Male

Female

PWIDs: 20-40 years of age

2015 (N = 33,454)

https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/Converted_ChronicHCV_SurvRpt_Graphs.pdf.

Opioid Use Disorder Is Driving Acute HCV

HCV prevalence among PWID is estimated to be 70%−77%1

1. CDC. Surveillance for Viral Hepatitis—United States, 2015. https://www.cdc.gov/hepatitis/statistics/2015surveillance/pdfs/2015HepSurveillanceRpt.pdf. 2. Hagan H, et al. Am J Epidemiol.2008;168(10):1099-1109.

1 in 3 people who inject drugs acquires HCV infection in the first year of injecting2

HCV Cases Reported in Maryland by County

Hepatitis C Strategic Plan, Maryland Department of Health, 2019

HCV in Maryland by County per 100,000 Residents

Hepatitis C Strategic Plan, Maryland Department of Health, 2019

Changing Epidemiology of HCV in the US

CDC

March 2020: The USPSTF now

recommends routine screening for all adults in the United States 18-

79 years of age

Natural History Following HCV Infection

https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all.

Time20-25 years

25-30 years

HCCESLDDeath75% to 85%

20% to 30%

2% to 7% per year

HCV Infection

Diagnosis, Treatment, and Monitoring

Diagnosis

HCV Therapy: 1991-Present

• IFN = Interferon

• Peg IFN = Pegylated Interferon

• RBV =Ribavirin

Sust

aine

d Vi

rolo

gic

Res

pons

e (%

)

IFN6 mos

PegIFN/ RBV

12 mos

IFN12 mos

IFN/RBV12 mos

PegIFN12 mos

IFN/RBV6 mos

0

20

40

60

80

100

DAA Combo

200119981991 2011 2015

When and in Whom to Initiate HCV Therapy

https://www.hcvguidelines.org..

Treatment is recommended for all patients with chronic HCV infection

Rating: Class I, Level A

Rationale for HCV Treatment

Reduce decompensated liver disease/hepatocellular carcinoma

Reduce cirrhosis

Reduce transmission and progression

Cirrhosis

Intermediate stages of fibrosis

Early stages of fibrosis

Rationale for HCV Treatment

Hepatitisc.uw.edu

Virologic Targets of Treatment

Hadgan, JAMA, 2011

HCV Treatment Regimens

https://www.hcvguidelines.org.

RegimenGenotype

1a 1b 2 3 4 5 6

Elbasvir/grazoprevir ü ü ü

Ledipasvir/sofosbuvir ü ü ü ü ü

Sofosbuvir/velpatasvir ü ü ü ü ü ü ü

Glecaprevir/pibrentasvir ü ü ü ü ü ü ü

Pre-Treatment Workup

Fibrosis

• FIB-4, Transient elastography, FibroSure, clinical, prior biopsy

DDI

• AASLD/IDSA guidance• University of Liverpool drug

interaction checker

Labs

• Platelets, INR• eGFR• Hepatic Function Panel• HCV RNA• HIV Ag/Ab• Hep Bs Ag• bHCG (serum or urine

pregnancy)

“Simplified Treatment”

Do use in:• Treatment naïve• Non cirrhotic patients

Do not use in: • Known or suspected hepatocellular carcinoma• Prior liver transplantation• HBsAg positive• Current pregnancy• HIV positive

“Simplified Treatment” First-Line Agents

Glecaprevir (300mg)/Pibrentasvir (120mg)

Mavyret

Sofosbuvir (400mg)/Velpatasvir (100mg)

Epclusa

Factors to Consider in Initial Treatment

SOF/VEL: • 12-week duration• Single pill• With or without food• Bottle

GLE/PIB: • 8-week duration• Three pills daily• Taken with food• Box

Insurance PreferenceLength of treatment

Pill burdenPackaging

Food Availability

On Treatment Monitoring

• Check in in some way (phone, telemedicine, in person) at least once

• Ask about adherence

• Ask about common adverse events

• NO LABS NEEDED if everything is going smoothly

Assess Sustained Virologic Response (Cure)

12+ weeks after last pill taken, obtain HCV VL

Positive = Relapse or Reinfection

Negative = Cure

New Data: MINMON Study

N=39995% SVR

CROI Virtual 2021 Abstract 135, Soloman

Post Treatment Monitoring After Cure

For low-risk individuals

<Stage 3 fibrosis

No reinfection

risksNothing!

For individuals

with advanced fibrosis

Stage 3-4 fibrosis

HCC screening

Variceal screening (Stage 4)

For high-risk groups

PWID, MSM, HIV+

Obtain yearly HCV

VL

Non-Cure: Definitions

Treatment Failure (Relapse)

• Detectable VL at SVR, of same genotype• Can be re-treated with alternative regimens

Reinfection

• Identified by a genotype switch• Can be treated as if initial infection

Non-Cure: Don’t Worry!

• >90% efficacy with re-treatment regimens• Address the initial cause of relapse

• Drug-drug interactions• Adherence• Life instability/challenges

Viral relapse will occur!

• Sign you are in the right population• Harm reduction is the key

Reinfection will occur!

Treatment in “Special” Populations

95 98 96 9899 95 99 99

0102030405060708090

100

SOF/VEL EBR/GZR LDV/SOF GLE/PIB

HIV/HCV HCV

Patie

nts

With

SVR

12, %

HCV Cure in HIV/HCV Coinfection

1. Wyles D, et al. Clin Infect Dis. 2017;65(1):6-12; 2. Feld JJ, et al. N Engl J Med. 2015;373(27):2599-2607; 3. Rockstroh JK, et al. Clin Infect Dis. 2018;67(7):1010-1017;4. Zeuzem S, et al. Ann Intern Med. 2015;163(1):1-13; 5. Naggie S, et al. N Engl J Med. 2015;373(8):705-713; 6. Afdhal N, et al. N Engl J Med. 2014;370(20):1889-1898; 7. Rockstroh JK, et al. Clin Infect Dis. 2018;14;67(7):1010-1017; 8. Asselah T, et al. Clin Gastroenterol Hepatol. 2018;16(3):417-426.

1,2 3,4 5,6 7,8

HCV Cure in People with OUD on MOUD

94 94 96 96 9296 97 98 96 95

0

20

40

60

80

100

OST no OST

OBV/PTV/r + DSV + RBV2

SOF/VEL/VOX5SOF/VEL4 GZR/ELB6,7SOF/LDV + RBV3

SVR

12, %

1. Grebely J et al. Nat Rev Gastroenterol Hepatol. 2017;14:641-651. 2.Grebely J. 2017 International Liver Congress (ILC 2017). FRI-236. 3. Grebely J et al. Clin Infect Dis. 2016;63:1405-1411. 4. Grebely J et al. Clin Infect Dis. 2016;63:1479-1481. 5. Grebely J. ILC 2017. FRI-235. 6. Zeuzem S et al. Ann Intern Med. 2015;163:1-13. 7. Dore GJ et al. Ann Intern Med. 2016;165:625-634.

MOUD No MOUD

0

10

20

30

40

50

60

70

80

90

100

Positive Drug Screen Negative Drug Screen

SVR1

2, %

(95%

CI)

123136

6165

90.4(84.2−94.8)

93.8(85.0−98.3)

HCV Cure in People Who Use Drugs (C-EDGE Co-STAR)

1. Rockstroh JK. European Association for the Study of the Liver. The International Liver Congress™ − EASL 2017. April 19-23, 2017; Amsterdam, The Netherlands; 2. Dore GJ, et al. Ann Intern Med. 2016;165(9):625-634.

Patie

nts W

ith P

ositi

ve

Urin

e Dr

ug S

cree

n, %

60

Baseline

Any Drug50

40

30

20

10

0Week

4Week

8Week

12FU4

FU12

FU24

Cocaine

OpiatesBenzodiazepines

OxycodoneAmphetamines

Res

pond

ers,

%

97 94

0

10

20

30

40

50

60

70

80

90

100

ETR SVR12

HCV Cure in People Who Inject Opioids(SIMPLIFY)

ETR, end of treatment; SOF/VEL, sofosbuvir/velpatasvir. Grebely J, et al. Lancet Gastroenterol Hepatol. 2018;3(3):153-161.

100103

97103

SOF/VEL x 12 Weeks

Challenges and Strategies in HCV Treatment

HCV Care Continuum in the United States

Yehia BR et al. PLoS One. 2014.

TimeTime

Patie

nts,

%

0

100

HCV Infected

Diagnosedand

Aware

Access to

Care

HCV RNAConfirmed

Liver Biopsy

Prescribed HCV

Treatment

AchievedSVR

100

5043

2717 16

9

• Insufficient number of providers who can treat HCV•Insufficient resources for case managers/social workers•Segregated service delivery•Cost of medications

Structural

•Provider knowledge of treatment guidelines•Provider knowledge of harm reduction•Patient–provider interactions•Provider reticence to treat PWID

Provider

•Limited knowledge about long-term consequences of HCV•Asymptomatic disease•Fear of side effects•Competing health and social priorities

Patient

HCV Treatment Barriers

Clinicians’ Assumptions Contribute to Barriers to Care

American Association for the Study of Liver Diseases (AASLD) survey. The Liver Meeting® 2016 – AASLD. November 11‒15, 2016; Boston, MA.

4

45

4

41

6

05

101520253035404550

Concerns AboutTreatment Response

Concerns AboutAdherence

Concerns AboutAdverse Events

Reinfection Risk Cost

Res

pond

ents

, %

Principles to Improve the HCV Care Continuum

Incorporate Harm

Reduction Framework

Collocate Services

Decentralize Services

Disregard for the disease model of addiction

Misconceptions about MOUD

Criminalization of substance use disorder

Addressing Stigma and Discrimination

Harm Reduction Framework

Slide courtesy of PeerView/Rachel McClean MPH

Streets, encampments,and freeway overpasses

Shelters and residential drug treatment programs

Methadone clinics/opiate treatment programs

Syringe services programs

Harm Reduction Framework

Multiple phone numbers(cell, friends, family)

Social media accounts (if OK to contact)

Programs, shelters, food pantries

Hangouts, sleeping spots

Collocate Services: Linkage and Retention

Slide courtesy of PeerView/Rachel McClean MPH

Pay-as-you-go phones

Appointment reminders and multiple opportunities for reengagement

Transportation, accompaniment, and advocacy

Benefits and insurance enrollment

Help getting IDs

Collocate Services: Testing

1. Healio. 2018. https://www.healio.com/hepatology/hepatitis-c/news/print/hcv-next/%7B50ee3be8-c17e-4101-97d5-398fb1b3fd7d%7D/treating-people-who-inject-drugs. 2. Hsieh YH, et al. J Viral Hepat. 2018.

•MAT facilities•Syringe services programs

•Emergency departments

•Homeless shelters

•Testing by secondary exchangers

•Linkage by peer navigators

•Fingerstick/point of care•Dried blood spot•Same-day RNA testing

Increase mobility and

speed of testing

Createpeer-based

services

Test in culturally competent locations

Test in locations frequented by

PWID

Collocate Services: TreatmentANCHOR Study

D, day; HIV, human immunodeficiency virus; PrEP, HIV preexposure prophylaxis; OAT, opioid agonist therapy; PWID, people who inject drugs; SOF, sofosbuvir; SVR12, sustained virologic response at ≥12 weeks after end of treatment; VEL, velpatasvir; W, week.Rosenthal ES, et al. Clin Infect Dis. 2020 (Epub ahead of print).

SOF/VEL Monitor for HCV reinfection

Buprenorphine (optional)

Risk-taking behavior assessment

D0

W4 W12

W24

W48

W72

W96

PrEP (optional)

HCV Cure in ANCHOR Study

Cured82%

Virologic Failure11%

Lost to Follow-up4% Dead

3%

OAT Uptake and Impact on HCV Cure in ANCHOR

OAT Uptake Impact of OAT on SVR at Week 24

Rosenthal ES, et al. Clin Infect Dis. 2020

91

63

0102030405060708090

100

OAT at week 24 No OAT at week 24

P=0.001

37 (70%) retained on OAT at week 24

53 (79%) started on OAT

67 (67%) patients not on OAT at baseline

100 PWID with OUD started on HCV treatment

Providers

Task shifting to• Specialists• Drug and alcohol specialists• Primary care providers • Nurses• Pharmacists• Peer support workers• Others

Decentralize Treatment

1. Akiyama M, et al. Ann Intern Med. 2019;170(9):594-603; 2. Beste LA, et al. Am J Med. 2017;130(4):432-438 e3; 3. Morey S, et al. J Viral Hepat. 2019;26(1):101-108.

Settings

Drug andalcohol clinics

Primary care clinics

Prisons

FQHCsSSPSexual health clinics

Pharmacies

Decentralize Treatment: ASCEND Study

All patients, ITT (P=0.19) All patients, per protocol (P<0.49) Cirrhosis, per protocol (P=0.69)

0

20

40

60

80

10091%

87%92%

Overall

93%

NP PCP Specialist

92%94% 95% 95%86% 89% 86% 83%

513600

513548

99109

135151

135142

2630

138160

138146

2527

240289

240260

4852

SVR

12 (%

)

Kattakuzhy S, et al. Ann Intern Med. 2017;167:311-318.

No difference in SVR of HCV treatment provided by NP, PCP, and specialist providers after a targeted 3-hour training

Key Points

• Hepatis C incidence is rising due to the epidemic of opioid use disorder

• All adults 18+ should be screened for HCV

• Initial treatment of HCV in non-cirrhotic patients is straightforward

• Primary care providers can and should treat HCV

• Improving care for patients with OUD and HCV requires a harm reduction framework, collocation, and decentralization

• The syndemic framework of care will improve outcomes across diseases

Thank [email protected]