HCV Elimination in PWIDs

and the Incarcerated

Supported by an independent educational

grant from Gilead Sciences Medical Affairs

Simply Speaking® Hepatitis “HCV Elimination in PWIDs and the Incarcerated” is

Copyrighted 2020 by Practice Point Communications, unless otherwise noted.  All rights reserved.
Content Development Faculty
Mark Sulkowski, MD
Professor of Medicine
Johns Hopkins University School of Medicine
Medical Director, Viral Hepatitis Center
Johns Hopkins Hospital
Baltimore, Maryland

• Disclosures
- Employment/Salary: None
- Research Grants/Investigator: AbbVie, Gilead Sciences
- Consultant: None
- Speakers Bureau, Faculty, Peer Reviewer: None
- Advisory Committee/Board: AbbVie, Gilead Sciences
- Stockholder: None
- Royalty: None
- Honoraria: None
2
- Other: None
Learning Objectives
(CME/CNE/CPE)

• Upon completion of this educational activity, participants should be better able to:
– Select appropriate anti-hepatitis C (HCV) regimens in HCV-infected patients who are candidates for therapy
according to the American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society
of America (IDSA) recommendations
– Discuss strategies to optimize harm reduction among persons who inject drugs

– Select appropriate screening and management approaches for HCV in incarcerated persons

3
Overview

• Critical populations impacting HCV elimination plans

• Persons who inject drugs

• The incarcerated

4
Update on WHO HCV Elimination 2030 Targets

• 2030 targets
Global Progress Towards Meeting
– 90% diagnosed WHO HCV Elimination Targets
2019 Status
– 80% treated
– 65% reduced mortality
– 90% reduction in HCV incidence

• HCV infection in United States: 2.9 million

• United States is not on track to meet all targets On track
by 2030 (extrapolated from 2019 data) Working towards
Not on track

Countries on track to met targets: Egypt, France, Ireland, Spain, Switzerland.

5
The Polaris Observatory HCV Collaborators. 1/2020. https://cdafound.org/dashboard/polaris/dashboard.html.
 United States (2019 Data):
Progress Towards Meeting WHO HCV Elimination Goals

2030 target Actual (2019)

100% 100% 100% 100%
100
90% 90%

80 80%
68%
Percent (%)

60

40 37%

20
10%

0
HCV Diagnosed HCV Treated Blood Injection Syringes/
Cumulative Cumulative Safety Safety PWIDs
(% of 300)

The Polaris Observatory HCV Collaborators. 1/2020. https://cdafound.org/dashboard/polaris/dashboard.html. 6

CDC (2013-2016):
Estimated HCV Prevalence Among Adults in the United States

HCV RNA Prevalence Total Persons With HCV RNA

(1.0%) (2.4 million adults)
Prevalence (per 100 population) Persons with HCV RNA (number)
0.45-0.65 0.65-0.85 0.85-1.00 1.00-1.25 1.25-2.34 2.6K-10K 10K-25K 25K-50K 50K-75K 75K-319K

7
Rosenberg ES, et al. JAMA Netw Open. 2018;1:e186371.
U.S. Preventive Services Task Force: Updated
Citation
Recommendations for HCV Screening

• All adults aged 18 to 79 years should be screened for HCV

– Includes asymptomatic adults (including pregnant women)
without known liver disease
– 1-time screening for most adults (periodic screening for
persons with continued risk of HCV infection)
– Expands the population to be screened beyond adults born
between 1945 and 1965 and others of high risk
• Suggests consider screening persons <18 and >79 years
of age who are at high risk for infection (eg, current or past
injection drug use)
– Limited evidence to determine how often to screen
Important Considerations
• Communicating that screening is voluntary and
undertaken only with the patient's knowledge
• Informing patients about HCV infection
– How it can (and cannot) be acquired
– Meaning of positive and negative test results
– Benefits and harms of treatment
• Providing patients the opportunity to ask
questions and to decline screening

8
United States Preventive Services Task Force. JAMA. 2020;323:970-975.
Critical Populations Impacting HCV Elimination Plans
in the United States

• PWIDs
– Represent the majority of persons with HCV (~70%)

– ~50% of PWIDs have been exposed to HCV

• <25 years of age: 25%

– Nearly 60% of PWIDs have a history of incarceration

• Incarceration and HCV

– Seroprevalence of HCV infection: 17% to 23%

– ~30% of all persons with HCV infection in the United States spend at least 1 year in a correctional institution

Verna EC, et al. JHEP Rep. 2019;1:240-255.

Stone J, et al. Lancet Infect Dis. 2018;18:1397-1409.
Ocal S, et al. Curr HIV/AIDS Rep. 2020;17:18-25.
Coyle C, et al. Hepatology. 2019;70:476-486.
AASLD-IDSA. http://www.hcvguidelines.org/full-report-view. Version November 6, 2019. 9
Overview

• Critical populations impacting HCV elimination plans

• Persons who inject drugs

• The incarcerated

10
CDC (2017):
Age-Adjusted Drug Overdose Deaths in the United States

• Drug overdose deaths in 2017 (n=70,237)

Drug Overdose Death Rates (2017)
– Age-adjusted rate: 21.7 per 100K
Drug overdose deaths (per 100K)
• 9.6% increase form 2016 6.9-13.5 13.6-18.5 18.6-21.0 21.1-58.0

• Opioids accounted for 68% of all drug

overdose deaths
– Mainly synthetic opioids (eg, fentanyl, tramadol)

• Highest drug overdose death rates (per 100K)

– West Virginia (57.8)

– Ohio (46.3)

– Pennsylvania (44.3)

– District of Columbia (44.0)

– Kentucky (37.2)
11
CDC, November 2019. https://www.cdc.gov/drugoverdose/pdf/pubs/2019-cdc-drug-surveillance-report.pdf.
Opiate Use Disorder and HCV Infection: Overdose Prevention
Should Be Incorporated Into Curative HCV Treatment

• C Change Philadelphia
History of Unintentional Overdose
– Survey of PWUDs enrolling in state designated opioid
centers of excellence and the city’s syringe exchange 50
programs

C Change Participants (%)

• Interim analysis on drug use behaviors and 40 39%
overdose risk (n=667; 50% with HCV infection)
– Male (68%), <30 years of age (15%) 30
– Homeless/unstable housing (58%), history of
incarceration (82%) 21%
20
– History of IDU (79%), currently using any drugs (56%)
≥3 Overdoses ≥3 Overdoses
• Risk of opiate overdose(s) is high in this cohort 10 (46%) (49%)

– Underscores the need to link PWUD to harm reduction

in conjunction with HCV treatment 0
HCV Ab HCV Ab
Positive Negative
12
Trooskin SB, et al. AASLD/EASL HCV Special Conference. Miami, 2019.
Viral Infectivity of HCV and Infection Equipment

• Viral infectivity of HCV persists for up to

Meta-Analysis: Risk of HCV Seroconversion
– 63 days in syringe barrel and dead space With Sharing Injection Equipment
– 21 days in water in a plastic container Pooled RR of HCV Population
Seroconversion Attributable
– 14 days on inanimate surfaces (ie, cookers and (95% CI) Risk* (%)
injection surfaces) Syringe sharing 1.9 (1.5-2.5) 25%
– 24 hours in filter and 48 hours when foil wrapped
Drug cooker sharing 2.4 (1.9-3.1) 43%
• Meta-analysis results provide strong support for Filtration cotton sharing 2.6 (1.9-3.6) 42%
current harm reduction recommendations
Rinse water 2.0 (1.5-2.6) 31%
– Include access to sterile syringes and drug
preparation equipment, and safe injection
education programs

*Population attributable risk represents the percentage of seroconversions that

could have been avoided if sharing was eliminated among PWIDs.
Doerrbecker J, et al. J Infect Dis. 2013;207:281-287.
13
Pouget ER, et al. Addiction. 2012;107:1057-1065.
Dynamic HCV Transmission Model in PWIDs

No SVR Not Cured

SVR HCV Infected
Allow for
Re-Infection
DAA
Therapy

New No Chronic HCV

PWID HCV Infection Infection

Spontaneous
Clearance

Cease/
Die
Acute HCV
Infection

14
 Countries With Greatest Total Number of People With
HCV Viremic Infection Among Recent Injection Use

10
~6.1 Million With Recent Injecting Drug Use Globally
Viremic Prevalence: 39.2%
Number With HCV Infections (100K)

0 Russia United Chile Brazil Japan Canada Italy Malaysia Indonesia Pakistan Mexico Viet Germany Georgia India Iran Romania Kazakh- England Afghani- France Australia
States Nam stan stan

Size of circle relates proportion of people living with HCV infection among all people with recent drug use.
Data were not available for Ukraine, Tanzania, and Myanmar to calculate the total proportion of viremic HCV infections among recent injection use.
Grebely J, et al. Addiction. 2019;114:150-166. 15
 New
Slide
Chronic HCV Cases in the United States (2018)

• National Notifiable Diseases Surveillance

System confirmed chronic HCV cases in Bimodal Distribution of Chronic HCV Cases in 2018
Among Males and Females
2018 (n=137,713)
– Males (63%) and females (37%): bimodal
distribution
• Distribution by generational age (rate per
100K population)
– Born after 2012: 0.1% (1.0)

– Born 1997-2012: 2.3% (6.1)

– Born 1981-1996: 37% (89.7)

– Born 1996-1980: 23% (66.7)

– Born 1945-1965: 36% (79.8)

Age (years)

Ryerson AB, et al. MMWR Morb Mortal Wkly Rep. 2020;69:399-404. 16

Changing Trends: Updated
Slide
Acute HCV in the United States (2009-2018)

• New acute HCV infections in 2018 Acute HCV Rate in US 2001-2018

3.5 Age group (years)
– Reported cases (n=3621)
20-29
3 30-39
– Estimated (n=50,300, adjusted for under-

Rate (per 100,000 population)

40-49
ascertainment and under-reporting) 50-59
2.5 ≥60
• 3-fold increase in new cases since 2009
2
– Reflects new infections associated with rising rates
of injection-drug use 1.5

• Most newly acquired acute HCV infections 1

occurred among young, white, PWIDs, who live
in non-urban areas (ie, Appalachian, 0.5

Midwestern, and New England states) 0

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
Year

Ryerson AB, et al. MMWR Morb Mortal Wkly Rep. 2020;69:399-404. 17

CDC:
National HCV Progress Report 2020 Goals

• Rate of acute HCV infections has increased Goal: Reduce the Rate of Acute HCV
since 2010 Infections to 0.25 per 100K Population
1.2
• Injection drug use is the most common risk
1.04
reported for persons with HCV infection 1 0.98

Cases per 100K Population

– Increases in HCV incidence are temporally
0.81
associated with increases in injection drug use 0.8
0.72 0.73

0.6 0.60

0.42
0.4
0.29

0.2 Goal
0.25

0
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

CDC. National Viral Hepatitis Progress Report 2020. https://www.cdc.gov/hepatitis/policy/NationalProgressReport.htm. 18

AASLD-IDSA Guidelines:
PWIDs

Recommendations
Annual HCV testing for PWIDs with no prior testing, or past negative testing and subsequent injection drug use
(depending on the level of risk, more frequent testing may be indicated)

Substance use disorder treatment programs and needle/syringe exchange programs should offer routine, opt-out HCV-antibody
testing with reflexive or immediate confirmatory HCV-RNA testing and linkage to care for those who are infected

Counsel about measures to reduce the risk of HCV transmission to others

Offer linkage to harm reduction services when available, including needle/syringe service programs
and substance use disorder treatment programs

Active or recent drug use or a concern for reinfection is not a contraindication to HCV treatment

At least annual HCV-RNA testing for PWID with recent injection drug use after they have spontaneously cleared HCV infection
or have http://www.hcvguidelines.org/full-report-view.
AASLD-IDSA. been successfully treated Version November 6, 2019. 19
AASLD-IDSA Guidelines:
Management of Acute HCV Infection

• Pre-exposure or post-exposure prophylaxis with antiviral therapy is not recommended

• In the setting of acute HCV infection

– HCV treatment should be initiated without awaiting spontaneous resolution
• Owing to high efficacy and safety, the same regimens that are recommended for chronic HCV infection are
recommended for acute infection
– Counseling to avoid hepatotoxic insults, including hepatotoxic drugs (eg, acetaminophen) and alcohol
consumption, and to reduce the risk of HCV transmission to others
– Referral to an addiction medicine specialist if acute HCV infection is related to substance use

AASLD-IDSA. http://www.hcvguidelines.org/full-report-view. Version November 6, 2019. 20

Sobriety Restrictions:
Medicaid Access (11/2018)

• No restrictions (n=13) and screening and

counseling (n=19): 64% of states Sobriety Restrictions (11/2018)
Restrictions
• Abstain restrictions: 36% of states None Screening/counseling
Abstain (months): 1 3 6
– 1 month (n=2)

– 3 months (n=6)

– 6 months (n=12)

21
Center for Health Law and Policy Innovation. https://www.chlpi.org/wp-content/uploads/2013/12/HCV-State-of-Medicaid-Access-Update-11-8-18.pdf.
Impact of Medicaid Abstinence Policies on DAA Prescriptions

• Analysis of the Medicaid Drug Utilization

DAA Prescriptions by Changes
File for each state (2014-2016) in Abstinence Policy
– 32 states with known abstinence 100 Maintained high restriction Changed to less restrictive

Prescriptions per 1000 HCV Infected

requirements in 2014 and 2016 Maintained no-to-low restriction Changed to more restrictive

• Increases in the use of DAAs by Medicaid 80

enrollees were significantly associated with

changes in state Medicaid programs’ 60
treatment eligibility criteria
40

20

High restriction: any documentation of abstinence from substance use. 0

Q2 Q4 Q2 Q4 Q2
No-to-low restriction: no documentation needed.
2014 2014 2015 2015 2016
Less restrictive: a change from high restriction to no-to-low restriction.
More restrictive: a change in the opposite direction.
Kapadia SN, et al. Clin Infect Dis. 2018;66:1618-1620. 22
Integrated Analysis of 7 Phase 3 Trials:
Glecaprevir/Pibrentasvir and Recent Drug Use
• Retrospective analysis of recent, past, or no drug use
(n=1819) Baseline Characteristics
– HCV treatment-naïve or -experienced (pegIFN/RBV, Recent Former Non-
PWUD PWUD PWUD
sofosbuvir + RBV ± pegIFN) (n=98) (n=610) (n=1111)
– Urine drug screening at baseline, self-reported drug use Male (%) 81 65 50
during studies
Age (years) 45 51 54
– No decompensated cirrhosis or HBV White/black/Asian (%) 84/12/1 90/5/3 73/6/19
– Analysis did not differentiate between injection and non- HCV RNA (log10 IU/mL) 6.0 6.2 6.1
injection drug use Genotype 1/3 (%) 46/39 45/40 57/13
• HCV regimen Compensated cirrhosis (%) 12 11 9

– Glecaprevir/pibrentasvir for 8 or 12 weeks Opioid substitution therapy (%) 31 15 <1

Positive urine drug screen (%)
• Outcomes Opioids/heroin 66/20 0/0 0/0
Other 46 0 0
– Achievement of SVR12, ≥90% adherence to treatment Cocaine 29 0 0
Amphetamine 29 0 0
Pooled data from ENDURANCE 1-4 AND EXPEDITION 1, 2, 4.
PWUD: persons who used drugs.
Foster GR, et al. Drug Alcohol Depend. 2019;194:487-494. 23
Integrated Analysis of 7 Phase 3 Trials:
Glecaprevir/Pibrentasvir and Recent Drug Use

• Lower SVR12 with recent drug use (OR 6.8; P=0.01)

SVR12 Rates (ITT)
• Virologic failure ≤2% of treatment completers
regardless of drug use status 100 97%* 99%*
93%*
• Non-virologic failure
80
– Recent (6%), former (2%), and non-PWUD (1%)

– Reinfection (n=1; former PWUD)

SVR12 (%)
60
• No difference in those ≥90% adherent (≥96%) or
completing therapy (≥97%) 40
Relapse Relapse Relapse
• Regimen was well tolerated (n=1) (n=6) (n=2)

– Discontinuations due to adverse events: ≤1% 20

91 561 1106
– Treatment-related serious adverse events (n=1) 98 610 1111
0
– Death (n=5; 1 due to drug overdose [recent PWUD]) Recent Former Non-
*P<0.0001 versus non-PWUD. PWUD PWUD PWUD
PWUD: persons who used drugs.
Foster GR, et al. Drug Alcohol Depend. 2019;194:487-494. 24
SIMPLIFY:
Sofosbuvir/Velpatasvir in PWIDs With HCV

Phase 4 study
Single-arm, open-label
Recent drug use (previous 6 months)
Sofosbuvir/Velpatasvir
HCV treatment-naïve or experienced (n=103)
HCV genotype 1-6
HCV RNA ≥1000 copies/mL Week 0 12
No HIV or decompensated cirrhosis
Hazardous alcohol use in past month (17%).
Any non-injecting drugs in the past month (54%).
Any injecting drug use in past month (78%):
Heroin (55%).
Cocaine (13%).
Methamphetamine (30%).
Other opioids (21%).
Other (7%).
History of opioid substitution therapy (82%).
Primary outcome: SVR12 (HCV RNA <12 IU/mL).
Baseline demographics: Current opioid substitution therapy (59%).
Male: 72%. Injected at least daily in the past month (26%).
Age: 48 years.
Unstable housing: 23%.
HCV genotype 1/2/3/4: 35%/5%/58%/2%.
HCV RNA: 6.1 log10 IU/mL.
ALT: 61 IU/L.
Liver disease:
F0-F1/F2-F3/F4: 61%/28%/9%.
Grebely J, et al. Lancet Gastroenterol Hepatol. 2018;3:153-161. 25
SIMPLIFY:
Sofosbuvir/Velpatasvir in PWIDs With HCV

• Overall SVR rate (ITT): 94% (97/103)

Daily Adherence
– No virologic failures or relapse
Dose received
– Reinfection (n=1; 2.6 cases per 100 person-years) No dose received
Discontinuation
• Completed treatment (n=100)
– Lost to follow-up (n=2), drug overdose (n=1)

• Considerable variation in adherence

– Median adherence: 94%

– >90% adherent: 66%

• Overall the regimen was well tolerated

– Serious adverse events (n=7; 1 [rhabdomyolysis]
was possibly related to treatment

Grebely J, et al. Lancet Gastroenterol Hepatol. 2018;3:153-161. 26

VA Cohort: Elbasvir/Grazoprevir in Patients Who Receive
Opioid Substitution Therapy

• Retrospective analysis (n=611; 2016-2017)

SVR12 Rate
– US VA Corporate Data Warehouse 100 97%
96% 96% 96%
– HCV genotype 1 with opioid use disorder or ≥1 prescription
for opioid substitution therapy 80
• Baseline characteristics
– Age (62 years), black (53%), male (96%), treatment-naïve 60

SVR (%)
(90%), genotype 1a (47%), HCV RNA >800K IU/mL (68%)
– Cirrhosis (35%), diabetes (34%), CKD stage 4-5 (85%), 40
drug/alcohol abuse (90%/77%), concomitant anti-
psychiatric medication (71%)
20
• SVR rates were high and comparable to phase 3
586 273 417 529
clinical trials 611 286 434 548
0
Overall Genotype Any Anti- History of
– Consistently high SVR12 rates across all subgroups 1a Psychiatric Drug Abuse
Medication

Kramer J, et al. J Hepatol. 2019;70(suppl):e112. Abstract PS-182. 27

HCV Continuum of Care Among PWIDs:
Philadelphia Department of Health

• Random sample of newly reported

HCV antibody positive persons HCV Continuum of Care Among
HCV Ab-Positive PWIDs
(n=29,820; 2013-2017) 100
– Interviewed and disclosed being a PWID 90% Years of age
85% >35 (n=1151)
(n=2390) 80
81%
≤35 (n=1239)
75%
• Measurable gaps exist in the HCV 66%

Patients (%)
continuum of care for PWIDs, especially 60

those ≤35 years of age

41%
40
– Among those HCV RNA positive
25%
• Only 29% and 10% of PWIDs >35 and ≤35
20
years of age, respectively, were treated
8%
• Need for enhanced navigation to services
0
Ever Tests for HCV RNA Initiated Treated
HCV RNA Positive HCV Care

Addish E, et al. Hepatology. 2018;68:929A-930A. Abstract 1632. 28

Strategies for Enhanced Linkage to Care
Venues Providing Access to Different
• Facilitated referral for HCV assessment and Substance Use Disorder Populations
scheduling of specialist appointment (ie, navigation
models)
Health Care System
– Peers, nurses, other health care workers as Primary Care, Tertiary Care, Opioid Replacement
Community Health Center,
navigators Outreach Mobile Clinic
Therapy Clinic

– Escort/transportation

• Mobile clinics Persons With

Substance Use
Disorder
• Embedded models within medication-assisted Correctional Needle Exchange
Facility Program
treatment, addiction, primary care programs

Detoxification
Center

Bajis S, et al. Int J Drug Policy. 2017;47:34-46.

Gonzalez SA, et al. Addict Disord Their Treat. 2017;16(2 suppl 1):S1-S23.
29
Gowda C, et al. Curr Hepatol Rep. 2018;17:111-120.
Interventions for Enhanced HCV Treatment

• Integrated HCV care, substance

use and psychiatric services
delivered by multidisciplinary team
• Biomarkers in place of liver
stiffness measurement
• DAA access

• Cash incentives

• Peer support

OAT: opioid agonist therapy.

DOT: directly-observed therapy.
NEPs: needle-exchange programs.
CBOs: community-based organizations.
Bajis S, et al. Int J Drug Policy. 2017;47:34-46.
Gowda C, et al. Curr Hepatol Rep. 2018;17:111-120.
30
Ward K, et al. Open Forum Infect Dis. 2019;6(4):ofz166.
CHAMPS Study: Impact of Cash Incentives and Peer Mentors
to Improve HCV Linkage and Treatment in HCV/HIV Patients

Randomized Controlled Trial

144 Participants (randomized 1:2:2)
HIV infection
HCV genotype 1 infections Usual Care, Received by All
No prior HCV treatment (Standard HIV clinic-based nurse model)
CD4 count >100 cells/mm3
No HCC or decompensated disease
Peer Mentor Care
(HIV/HCV trained mentors)

Cash Incentives
(Cash compensation*, contingent on attendance)

*Escalating scale: initial visit ($10) and increases $5 every 2 weeks to a maximum possible compensation of $220.
HCV treatment offered: ledipasvir/sofosbuvir for 12 weeks.
Baseline demographics:
Male: 61%.
Age: 55 years.
Black: 93%.
Urine for cocaine or heroin: 46%.
Cirrhosis: 12%.
Moderate to heavy alcohol use: 33%.
Depression: 61%.
On ART: 97% (80% with undetectable HIV RNA).
31
Ward K, et al. Open Forum Infect Dis. 2019;6(4):ofz166.
CHAMPS Study: Impact of Cash Incentives and Peer Mentors
to Improve HCV Linkage and Treatment in HCV/HIV Patients
• Despite removal of barrier, 33% of patients
assigned to usual care did not start HCV HCV Treatment Initiation and SVR12 Rates
Treatment initiation SVR12 in randomized patients
treatment SVR12 with ledipasvir/sofosbuvir
100
92% 91%
• No statistical difference in HCV treatment 90%
83%
initiation among the 3 groups 80 76% 76%
– Results may, in part, be explained by the 67% 69%

Patients (%)
61%
enhanced usual care in the clinic under study 60

• In settings where such resources are available, peer

mentors and/or cash incentives may have greater 40
impact on HCV outcomes
– Employed persons may not benefit from 20
additional interventions
• Data underscore the need for strategies to 0
Usual Care Peer Mentors Cash Incentives
increase HCV treatment initiation (n=36) (n=54) (n=54)
32
Ward K, et al. Open Forum Infect Dis. 2019;6(4):ofz166.
ANCHOR Study: Concurrent Initiation of HCV Treatment
and Opioid Agonist Therapy in PWIDs

• Prospective, open-label, observational study set at a harm

reduction organization drop-in center in Washington, DC Patient Enrollment and Disposition

Baseline Characteristics Enrolled

(n=100)
Patients (n=100)
Median age (years) 58
On OAT at No OAT at
Male (%) 76 Screening (n=33) Screening (n=67)
Black (%) 93
Cirrhosis (%) 33
Transferred Initiated OAT Initiated
Unstable housing (%) 51 OAT to Through Non-Collocated
ANCHOR ANCHOR OAT
Prior incarceration (%) 92 (n=3) (n=49) (n=4)

Government benefits/no income source (%) 42/50

≥Daily IDU (%) 59
Medication assisted treatment (%) 33
Receptive sharing of IDU equipment (%) 29 Always on Stopped Started Started Never on
OAT OAT OAT and OAT and OAT
Hazardous drinking (%) 40 (n=31) (n=2) Retained Stopped (n=14)
(n=37) (n=16)
OAT: opioid agonist therapy.
No decompensated cirrhosis or contraindicated DDIs
HCV regimen: sofosbuvir/velpatasvir for 12 weeks.
Rosenthal ES, et al. Clin Infect Dis. 2020;Feb 3. [Epub ahead of print]. 33
ANCHOR Study:
Results

SVR12 Rates Opioid Overdose

100 1
90% 92%

Opioid Overdose Free (%)

82% OAT
80 0.8
P=0.46
63%* 64%*
SVR12 (%)

60 0.6
50%
No
40 0.4 OAT

20 0.2

0 0
Overall Always Started Started Never Stop 0 29 71 127 183 239 300 365 425 505
(n=100) OAT OAT/ OAT/ OAT OAT
(n=31) Retained Stopped (n=14) (n=2)
(n=37) (n=16)
OAT: opioid agonist therapy. Time (days)
*P<0.5 versus started OAT and retained.
Rosenthal ES, et al. Clin Infect Dis. 2020;Feb 3. [Epub ahead of print]. 34
ANCHOR Study:
Conclusions

• High uptake of buprenorphine collocated with HCV treatment

– On buprenorphine (86%): at baseline (33%) or initiated prior to week 24 (53%)

• PWIDs had high rates of completion of DAA therapy and achieved high SVR12 rates

• Achieving SVR
– Not associated with baseline opioid agonist therapy, on-treatment drug use, or imperfect daily adherence

– Significantly associated with completion of at least 8 weeks of sofosbuvir/velpatasvir and being on opioid
agonist therapy at week 24
• Concurrent initiation of opioid agonist therapy with HCV treatment can result in high rates of SVR
while reducing risks associated with drug use

Rosenthal ES, et al. Clin Infect Dis. 2020;Feb 3. [Epub ahead of print]. 35
TraPHepC in Iceland: Impact of Universal Access to DAA
Therapy on New HCV Infections

• TraP HepC project (ongoing since 2016)

Key Outcomes With Universal Access
– All HCV RNA positive persons are offered DAA therapy
2015 (TraP HepC baseline) 2017
(n=749 enrolled, 722 initiated treatment; 2016-2019)
120
• Baseline demographics (first 631 participants) 55% 73%
Reduction Reduction
100

Number of Participants
– Mean age (43 years), male (67%), HCV genotype
3a/1a (58%/36%), home/halfway house (86%),
incarcerated (5%), homeless (6%) 80

– Ever/recent injected drugs (86%/33%), inject stimulants 60

(86%), medication-assisted therapy for opioid use
disorder (10%)
40
• SVR12 achieved on first attempt: 89%
20
• Universal access has led to a marked reduction of
HCV prevalence among PWIDs and the
0
incarcerated Admitted for PWID New HCV PWID HCV
Addiction Admitted Infections RNA Positive
TraP: treatment as prevention. Treatment
36
Runarsdottir V, et al. AASLD/EASL HCV Special Conference. Miami, 2019.
HCV Care Continuum+:
Preserving the Benefits of HCV Cure

• Risk of HCV reinfection post SVR should be part of the initial evaluation prior to HCV therapy

• Risk assessment
– Use to tailor an appropriate strategy of education, counselling, and linkage to services to help reduce risk of
subsequent reinfection

Post-SVR Care
Reinfection counseling
Linkage to harm reduction
Diagnosis Linkage to Care Treatment Cure
Surveillance
Reinfection surveillance
HCC surveillance
(Metavir F3/F4)
Counsel on Transmission/Reinfection Risk
Linkage to Harm Reduction
PWID: Needle/syringe services, opioid substitution therapy,
behavioral interventions
MSM: drug use, condoms, behavioral interventions

Falade-Nwulia O, et al. J Viral Hepatol. 2018;25:220-227. 37

C-EDGE Co-STAR Part B: Injection Risk Behavior in HCV
Patients on Opioid Agonist Therapy

Open-Label Extension of Primary Study

On opiate agonist therapy ≥3 months
HCV genotype 1, 4, or 6 Follow-Up (n=199)
Received ≥1 dose of elbasvir/grazoprevir in part A
(phase 3 study of elbasvir/grazoprevir 12 weeks)
Assessments every 6 months Month 0 12 18 24 36
HCV RNA
Urine drug screen
Self-reported drug use
Current Analysis on 149 Patients
Who Completed 30 Months of Follow-Up

SVR12 rate in Part A of study: 91% (269/296)

Baseline demographics of Part B:
Male: 76%.
Age: 49 years.
White: 79%.
Genotype:
1a/1b: 72%/20%.
4/6: 4%/1%.
Cirrhosis: 22%.
HIV-coinfected: 8%.
Grebely J, et al. Hepatology. 2018;68(suppl S1):35A. Abstract 52. 38
 C-EDGE Co-STAR Part B: Injection Risk Behavior in HCV
Patients on Opioid Agonist Therapy

80
Positive Urine Drug Screen
Baseline:
60% 59% 59% Follow-up (months): 6 18 30
60
53%
Patients (%)

40

27% 27% 28% 28% 29% 28%

23% 24% 23% 23%
21%
20
16%
12% 11% 13% 13%
8% 8%
6%
4%
0
Any Positive Amphetamines Cocaine Opioids Benzodiazepines Cannabinoids
Drug Screen

Grebely J, et al. Hepatology. 2018;68(suppl S1):35A. Abstract 52. 39

C-EDGE Co-STAR Part B:
Injection Risk Behavior in Patients on Opioid Agonist Therapy

• Part A (n=296)
Reinfection Rate
– HCV genotype 1, 4, or 6 on opiate agonist therapy 5
– Received elbasvir/grazoprevir: SVR 97%

Rate per 100-Person-Years

4
• Part B: open-label (n=149 with 30 months of follow-up)
– Reinfection rate: 1.8 per 100 person-years
3 2.8
– Number of reinfections (n=10: spontaneous clearance [2],
persistent infection [8; 4 re-treated and achieved SVR12])
2 1.8
• HCV reinfection among patients on opioid agonist therapy
following DAA therapy is uncommon, despite ongoing 1
drug use 0.3
0
Overall Yes No
Injection Drug Use

Grebely J, et al. Hepatology. 2018;68(suppl S1):35A. Abstract 52. 40

 Updated
Citation
HCV Reinfection Following SVR in PWIDs

• Meta-analysis (36 studies)

Factors Associated With HCV Reinfection
– Prospective (n=26), retrospective (n=10)
Adjusted
– Treatment setting: drug treatment service (36%), community Rate Ratio
(95% CI)
clinic (19%), tertiary care (8%), prison (6%), primary care (3%),
mixed setting (28%) Median/mean follow-up (per year increase) 0.94*
Versus opioid substitution therapy and no
• Reinfection rate (per 100 person-years) drug use
Drug use
– Recent injecting or non-injecting drug use: 5.9 With opioid substitution therapy 3.47*
No opioid substitution therapy 3.74*
– Recent injecting drug use: 6.2 Unknown use of opioid substitution therapy 6.81*
– Opioid substitution therapy ± recent drug use: 3.8
*P<0.001.
• Post-treatment HCV reinfection rate was associated with
recent drug use/opioid substitution therapy status
– Highest rate: recent drug use, not receiving OST

Hajarizadeh B, et al. J Hepatol. 2020;72:643-657. 41

Impact of Needle Syringe Programs and Opioid Substitution on
HCV Transmission
Current Opioid Substitution Therapy
50% reduction in HCV transmission
12 studies, 6361 participants, 1030 HCV cases.
Platt L, et al. Addiction. 2018;113:545-563.
Current Opioid Substitution Therapy and
High-Coverage Needle Syringe Programs
71% reduction in HCV transmission
4 studies, 3356 participants, 518 HCV cases.
42
Scandinavian Cohort (7-Year Follow-Up):
Incidence of HCV Reinfection After SVR

• Cohort of PWID from Norway, Sweden, Denmark

(North-C trial, n=428) Incidence of Persistent HCV Reinfection
– Abstinent >6 months before HCV treatment 5 4.9

Incidence (per 100 Person-Years)

– Genotype 2/3: SVR24 76%
4
• 12 cases of HCV recurrence after SVR among
Norwegians (n=138, follow-up >7 years)
3
– All were among the group who had relapsed to IDU
(n=44)
– None among the 94 who remained non-IDU 2
1.7
• HCV reinfection becomes relevant over time 1.2
1
– Might compromise long-term benefits of treatment for
patients with continuous risk behaviors
0
• Harm reduction intervention and education All Patients IDU IDU
(n=138) Ever Post SVR
– Essential for patients at highest risk of reinfection (n=94) (n=37)

PWID: people who inject drugs.

Midgard H, et al. J Hepatol. 2016;64:1020-1026. 43
Risk Factors for HCV Reinfection and Prevention
Considerations in PWIDs

Risk Factor for HCV Infection/Reinfection HCV Reinfection Prevention Intervention

Relapse to injection drug use Opioid substitution therapy, high-coverage needle/syringe
High frequency injection drug use including use of cocaine and methamphetamines programs, and behavioral change counseling for safer
Hospitalization for opiate and injection drug use related causes injection practices
Sharing injection use paraphernalia Other drug use treatment services

Shorter duration of injection Mental health services

Younger age (<30 years) Case management services for linkage to social services
Low levels of education (eg, housing, job programs)
Poor social functioning Peer-based programs to support safer injection practices
and drug use cessation

Continued injection drug use and sharing of drug use paraphernalia after HCV cure Treat drug use or high-risk network members for
Continued high-risk sexual practices after HCV cure HCV simultaneously
De-stigmatization of drug use, sexual practices, hepatitis
and HIV infection
Development of an effective HCV vaccine

Falade-Nwulia O, et al. J Viral Hepatol. 2018;25:220-227. 44

Priorities for Elimination of HCV Transmission
Detection
• HCV spreads quickly/quietly
among PWIDs
• Promote testing/reporting from
target settings (eg, drug treatment,
corrections, ED, OB/GYN)
• Revise testing/reporting policies
(eg, age, perinatal, etc)
• Investigate transmission networks
(lab/epi/behavioral science tools)
• Provide data to target response
Response
• Evidence based interventions can
stop transmission
• Need large increase in prevention
capacity
• Safe injection programs
• Substance abuse treatment (new
SAMHSA funds )
• HCV testing and curative therapy
as part of Cure and Prevention
strategies
• Community engagement
Research
• Improve implementation of
prevention strategies
• Engage PWIDs in HCV
prevention/care
(CDC/NIDA/SAMHSA/ARC study)
• Begin and complete HCV
treatment and prevent reinfection
(PCORI study)
45
Overview
• Critical populations impacting HCV elimination plans

• Persons who inject drugs

• The incarcerated

46
HCV Among Incarcerated Populations

• Global HCV prevalence

Selected Regional Prevalence in Prisoners
(2005-2015 data) (2005-2015)
– Among the incarcerated (46 countries) 25
HIV HBsAg
• 15.1% (1.55 million) HCV Active tuberculosis

20
• Regional range: 5% to 21%

Prevalence (%)
• North America: 15%
15
– Among PWID and incarcerated
(19 countries)
10
• Wide regional prevalence: 8% to 95%

• >40% for majority of countries 5

0
North Latin Western Eastern Asia
America America Europe Europe Pacific

Dolan K, et al. Lancet. 2016;388:1089-1102. 47

HCV Among Detainees and Prisoners in
Correctional Facilities in the United States

• Prevalence in state and federal correctional

Proportion of HCV-Infected State Prisoners
facilities Receiving Any HCV Treatment (2015)
Treated (%)
– 9.6% to 41.1% versus 1.8% in general population
No data ≤0.12 0.14-0.45 0.46-1.48 1.82-5.90
– Approximately 30% of all released prisoners have
HCV infection
• HCV screening
– Routine screening is rare, need for systematic plan
for HCV screening
• Inmates participating in health-related programs
while incarcerated
– Lower recidivism rates and more likely to maintain
health-conscious behaviors
Altice FL, et al. Curr Hepatitis Rep. 2004;3:112-118.
Maru DS, et al. Clin Infect Dis. 2008;47:952-961.
Beckman AL, et al. Health Aff. 2016;35:1893-1901.
Beck AJ, et al. Bur Justice Stat Bull. April 2004. https://www.bjs.gov/content/pub/pdf/httsp.pdf. 48
Role of Prisons in Concentrating, Amplifying, and Disseminating
Infectious Diseases

Concentration Amplification Deterioration

Prison Environment
Laws and policing selects members
with poor health status and/or at risk In High risk behaviors,
for HIV, TB, or viral hepatitis new social networks,
Out
transmission to new
community members

Community Dissemination
Post-Release
Morbidity and Mortality
Kamarulzaman A, et al. Lancet. 2016;388:1115-1126. 49
Meta-Analysis: Impact of Recent Incarceration on the Risk of
HCV Acquisition Among PWIDs

• Systematic review and meta-analysis (2000-2017)

Recent Incarceration and HCV Acquisition Risk
– Published (n=20) and unpublished (n=21) studies

– Australasia, western/eastern Europe, North/Latin America,

and east and southeast Asia
• Recent incarceration associated with increased
relative risk of HIV and HCV acquisition
– HIV acquisition: 1.81 (P=0.001)

– HCV acquisition: 1.62 (P=0.002)

• Past incarceration associated with increased relative

risk of HCV acquisition
– HIV acquisition: 1.25 (P=0.11)

– HCV acquisition: 1.21 (P=0.004)

50
Stone J, et al. Lancet Infect Dis. 2018;18:1397-1409.
Modeling Study: Impact of HCV Treatment in Scotland Prisons
on HCV Epidemic in PWIDs

• Incarceration contributes 28% of HCV

Projected HCV Risk Reduction Among
transmission among PWIDs in Scotland
All PWIDs (2015 to 2030)
– Sentence duration among incarcerated PWIDs 0

Relative Incidence Reduction (%)

• >12 weeks: 60% -10
-9% -10%
• >16 weeks: 43% -20
– Current DAA treatment rate (10.4 per 1000 -30
incarcerated PWIDs)
-40
• Over 15 years, treating 80% of HCV-infected
-46%
PWID prison entrants that have sentences -50

>12 weeks could decrease HCV prevalence -60 -56%

among all PWIDs by
-70
Community Continuing >16-Week >12-Week
– 56% (no reduction in HCV risk post-release) Treatment Status Quo Sentence Sentence
Only After With DAA*
Treat 80% of PWID
– 74% (prevention of HCV risk post-release) 2015
Prison Entrants

51
Stone J, et al. Addiction. 2017;112:1302-1314.
Outcomes of Treatment for HCV in Prisoners Using a
Nurse-Led, State-Wide Model of Care in Australia

• Prospective cohort of HCV infected

Decentralized, Nurse-Led Model of Care
prisoners (n=416)
– 82% of prisoners had never pursued
specialist HCV care in the community
– 18% of prisoners required specialist input

• Nurse‐led care was associated with

SVR12 rates of >95% in large numbers
of prisoners
– No difference in SVR rates between
nurse-led and specialist care

52
Papaluca T, et al. J Hepatol. 2019;70:839-846.
Virginia Department of Corrections:
HCV Treatment Experience

• Retrospective analysis of DAA therapy for

Outcomes and Baseline Characteristics
prisoners through telemedicine (2015)
Private
– Treatment regimens per AASLD guidelines Prisoners Insured Indigent
(n=84) (n=144) (n=96)
• Not treated if <9 months of sentence, recent
SVR12 (%) 95 93 95
drug/alcohol use, tattoos
Baseline characteristics
– HIV coinfection allowed (CD4 >100 cells/mm and 3 Age (years) 53 59 55
Male (%) 95 61 56
HIV RNA undetectable) White/black (%) 58/42 51/46 36/62
Advanced fibrosis (%) 100 92 67
– No decompensated cirrhosis, HBV, or HCC ALT (U/L) 86 100 78
FIB-4 score 3.8 5.0 4.0
• Similar SVR12 rates achieved among the 3 Treatment-experienced (%) 17 51 20
groups of patients despite differences in age, HIV coinfected (%) 4 4 2
RBV use (%) 88 44 16
gender, treatment experience, FIB-4, and use of
RBV

Prisoners, private insured, and indigent patients were treated by the same clinic/physicians.
53
Sterling RK, et al. J Correct Health Care. 2018;24:127-136.
Cost-Effectiveness and Budgetary Impact of HCV Testing, Updated
Citation
Treatment, and Linkage-to-Care in the United States

• Individual-based simulation modeling

Effectiveness, Cost, and Incremental Cost-Effectiveness
– Incorporates healthcare and Department of of 15 Models Tested

Corrections perspectives
• Compared to "no testing, no treatment, and no
linkage-to-care“
– “Test all, treat all, and linkage-to-care at release"
increased the lifetime SVR12 by 23%, reduced
cirrhosis cases by 54%
• DOC annual additional cost: $1,440/ prison entrant and
would be cost-effective

54
Assoumou SA, et al. Clin Infect Dis. 2020;70:1388-1396.
HEP C FREE LA: Updated
Slide
Louisiana HCV Elimination Plan (2019-2024)
• Plan to achieve HCV elimination in Louisiana by
the end of 2024 Establish HCV Treatment Subscription
Model for Medicaid and Corrections
• 7 strategies of the plan
– Establish HCV treatment subscription model for • Innovative drug pricing and payment mechanism that
Medicaid and corrections will enable Louisiana to dramatically expand access to
HCV treatment within its Medicaid and incarcerated
– Educate public on availability of cure and mobilize populations
priority populations for screenings
• Effectively caps the State’s spending on DAAs at 2018
– Expand HCV screening and linkage to HCV care levels while also creating an incentive to treat as many
– Strengthen active surveillance and scale-up data to
infected people as possible
HCV cure programs • Under the proposed agreement, unrestricted access will
– Expand provider capacity to treat HCV be provided to the authorized generic version of
sofosbuvir/velpatasvir for Medicaid eligible and
– Implement harm reduction and complementary incarcerated Louisianans for 5 years
treatment strategies
– Expand elimination efforts to all populations within
the state
55
August 2019. https://www.louisianahealthhub.org/wp-content/uploads/2019/08/HepCFreeLA.pdf.
Federal Bureau of Prisons:
Priority for HCV Treatment

High Priority Intermediate Priority Low Priority

• Advanced hepatic fibrosis • Evidence for progressive fibrosis • Stage 0-1 fibrosis on liver biopsy
- APRI ≥ 2.0, or – APRI score ≥0.7 • APRI <0.7
- Metavir or Batts/Ludwig stage 3/4
– Stage 2 fibrosis on liver biopsy • All other cases of HCV infection
on liver biopsy, or
- Known or suspected cirrhosis • Comorbid medical conditions meeting the eligibility criteria for
associated with more rapid treatment
• Liver transplant recipients
progression of fibrosis
• HCC
• Chronic kidney disease (eGFR
• Comorbid medical conditions
<59 mL/min)
associated with HCV
• Continuity of care for those • Birth cohort
already started on treatment

Federal Bureau of Prisons recommends:

Opt-out voluntary testing of all inmates for HCV infection, regardless of sentencing status, including new intakes and those already in population
who have not been previously tested.
Preferred HCV regimens currently recommended by the AASLD-IDSA.
56
Federal Bureau of Prisons. August 2018. http://www.bop.gov/resources/health_care_mngmt.jsp.
AASLD-IDSA Guidelines:
HCV Testing and Treatment in Correctional Settings

Recommendations
Jails
Implement opt-out HCV testing: HCV-antibody followed by confirmatory HCV-RNA testing if antibody-positive
If HCV infected, provide counseling and follow-up community linkage to care following release
Provide HCV treatment if sentence is of sufficient duration

Prisons
Implement opt-out HCV testing
Chronically infected prisoners should receive HCV therapy per AASLD-IDSA guidelines
Provide harm reduction and evidence-based treatment for underlying substance use disorder

Jails and Prisons

Facilitate continuation of HCV therapy for individuals on treatment at the time of incarceration

AASLD-IDSA. http://www.hcvguidelines.org/full-report-view. Version November 6, 2019. 57

HCV Drugs Save Lives, but Sick Prisoners Aren’t Getting
Them: The New York Times 2018

• Any national campaign to eliminate HCV, an insidious virus that kills tens of thousands of Americans
a year, would almost certainly involve prisons
• 1 in 7 state inmates are believed to be infected, and the regimented environment of a prison has its
advantages when it comes to screening and treatment
• In 2015 survey of state corrections departments
– Number of inmates with HCV (n=106,266)

– Inmates with HCV being treated: <1%

https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2016.0296. 58
HCV and the Incarcerated

• HCV prevalence is much higher than in the general community

• Correctional setting is an ideal setting for identifying HCV-infected persons

• Incarceration can be an ideal time to treat HCV infection

• Cost of HCV therapy and limited capacity of the correctional workforce

– Forced most correctional facilities to prioritize treatment based on disease severity

• Education, harm reduction, and prevention services are important to minimize the risk of reinfection
after achieving SVR
• All HCV-related cirrhosis need ongoing medical care before and after achieving SVR

• The partnering of correctional systems with public health systems is an important step in achieving
HCV elimination in the United States

59
CME/CNE/CPE Credit

• Please return to the CME/CNE/CPE activity page for the Simply Speaking Hepatitis Lecture
Library at www.PracticePointCME.com
– Click on the ‘Claim Credit’ button associated with this archived PowerPoint presentation

– Complete the brief posttest and evaluation form

– Upon successful completion of the posttest (ie, 80% accuracy), you will be able to print your CME/CNE/CPE
certificate for 1 credit hour
• Please visit us at www.PracticePointCME.com to review other archive presentations in the Simply
Speaking Hepatitis Lecture Library of interest and receive additional CME/CNE/CPE credit

60