Impact of Opioid Addiction on Hepatitis C Infection · Overall, individuals with HIV/HCV...

Impact of Opioid Addiction on Hepatitis C Infection

Shobha Joshi, MD

Disclosure

• Research Support: Intercept

• Speaker: AbbVie, Gilead, Intercept

Objectives

• Prevalence of Hepatitis C in Opioid addicted population

• Disease spectrum of hepatitis C in PWID

• Overcoming challenges in hepatitis C in PWID

• Value of Cure

• Treatment of hepatitis C in PWID

• WHO goals for eliminating hepatitis C and treatment guidelines for PWID

First Objective




• Value of Cure



Slide credit: clinicaloptions.com

0% to < 0.6%

0.6% to < 0.8%

0.8% to < 1.3%

1.3% to < 2.9%

2.9% to < 6.7%

Prevalence

(Viremic)

Polaris Observatory HCV Collaborators. Lancet Gastroenterol Hepatol. 2017;2:161-176.

Estimated 70 Million Persons Living With HCV

http://www.clinicaloptions.com/

Polaris Observatory HCV Collaborators. Lancet Gastroenterol Hepatol. 2017;2:161-176.

Blach S, et al. AASLD 2016. Abstract 753.Slide credit: clinicaloptions.com

50% of Total

80% of Total

To

tal V

ire

mic

In

fectio

ns (

Mill

ion

s)

12

10

8

6

4

2

0

30 Countries Account for 80% of HCV Infections


• Screening → linkage to HCV care → DAA treatment cascade must be operative in all those at risk

• Treatment of PWIDs plus harm reduction efforts essential part of elimination efforts

Slide credit: clinicaloptions.com

Male

Female

Mostly baby

boomers

Ne

wly

Re

po

rte

d H

CV

Ca

se

s (

%) 5

0 10 20 30 40

Age (Yrs)

4

3

2

1

0

50 60 70 80 90 100

New

ly R

ep

ort

ed H

CV

Ca

se

s (

%) 5

0 10 20 30 40

Age (Yrs)

4

3

2

1

0

50 60 70 80 90 100

Male

FemalePWIDs: 20-40

yrs of age

2007 (N = 41,037) 2015 (N = 33,454)

California Department of Public Health. Chronic hepatitis C infections in California:

cases newly reported through 2015. June 2017.

Changing Epidemiology of HCV in the US


Heroin use has increased among most demographic groups in the USA

Characteristics of PWID

Centers for Disease Control and Prevention. Today’s Heroin Epidemic. Available at: https://www.cdc.gov/vitalsigns/heroin/index.html (accessed August 2017) *<$20,000 per year; †$20,000–$49.999 per year; ‡>$50,000 per year

2002–2004 2011–2013vs.

2.4 3.6

0.8 1.6

Rate of heroin use (per 1,000 people)

Men

Women

2.4 3.6

0.8 1.6

18–25 years

≥26 years

White (non-Hispanic) 1.4 5.5

3.4 5.5

1.3 2.3

1.0 1.6

Low income*

Middle income†

High income‡

50%↑

100%↑

109%↑

58%↑

114%↑

62%↑

77%↑

60%↑4.3 4.7

0.8 1.3

Medicaid

Private

—

63%↑

• Greatest increases occurred in groups with historically low rates of heroin use: women, the privately insured, and people with higher incomes

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Prevalence of HCV among young PWID is increasing in USA

Epidemiology of HCV in PWID

Centers for Disease Control and Prevention. Viral Hepatitis and young people who inject drugs: https://www.cdc.gov/hepatitis/featuredtopics/youngpwid.htm (accessed August 2017)

PWID: people who inject drugs

▪ Most new HCV cases are among PWID▪ The number of new HCV infections has increased:

– 30 states reported increases >200% during 2010–2014

▪ The largest increases occurred among young persons in non-urban counties, particularly in Appalachian states

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Second Objective




• Value of Cure



New Hepatitis C Infections

• IDU accounts for the majority (70%) of new infections

• The high risk period is the first few years of IDU in an individual, infection rate exceeds 40%

Kinetics Acute HCV Infection with Recovery

HCV RNA

1 2 3 4 5 6 1 2 3 40

Months Years

Tite

r

Time after Exposure

ALT

anti-HCV

Normal

Symptoms +/-

Adapted from MMWR 1998; 47(No. RR19)

Adapted from Chen SL, Morgan TR. Int J Med Sci. 2006;3:47-52.

*20%-30% of individuals are symptomatic. HCC=hepatocellular carcinoma.

Acute Infection*Chronic

Infection75%-85%

Clearance of HCV RNA15%-25%

Extrahepatic Manifestations

Cirrhosis10%-20%

over 20 years

HCC1%-4% per year

Decompensated Cirrhosis

5-yr survival rate 50%

Natural History of HCV Infection

Survival probability in PWID co-infected with HIV/HCV

Kaplan-Meier estimate of survival probability by HCV status in PWID and HIV (Antiretroviral Therapy Cohort Collaboration study; 2000–2009)

Burden of HCV in PWID

May MT, et al. J Acquir Immune Defic Syndr 2015;69:348–54Data from the Antiretroviral Therapy Cohort Collaboration study, involving patients with HIV from 16 European and North American cohorts; HCV+ was defined as positive antibody test or plasma HCV RNA.

ART: antiretroviral therapy; HR: hazard ratio; IDU: injection drug user; PWID: people who inject drugs

▪ Overall, individuals with HIV/HCV co-infection have 2.5x greater mortality rates and higher rates of liver mortality (adjusted HR=14.0), compared with those without HCV

27,567506

17622868

23,729426

14852400

19,625353

12091958

15,919289953

1553

0.90

0.92

0.94

0.96

0.98

1.00

Years from start of ART

Surv

ival

pro

bab

ility

Log rank test P<0.0001

Number at risk:HCV– non-IDU

HCV– IDUHCV+ non-IDU

HCV+ IDU

0 1 2 3

HCV– non-IDUHCV– IDUHCV+ non-IDUHCV+ IDU

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• Value of Cure



What exactly do we mean when talking about PWID?

• A PWID is a person who may have:– Injected once– Injects regularly– Injects occasionally– On stable Opioid substitution

therapy (OST) and no longer injects

– Last injected 35 years ago

• It is important to understand the different populations as tailored HCV screening and management strategies are needed for different PWID populations

Characteristics of PWID

Larney S, et al. Int J Drug Policy 2015;26:950−7; Grebely J, Dore GJ. Antiviral Res 2014;104:62–72

NSP: needle/syringe programme;OST: opioid substitution therapy; PWID: people who inject drugs

Due to the relapsing nature of drug dependence, PWID often move between

populations and may access harm reduction services at any time

Lifetime PWID

OST

NSP

Active PWID

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NSP: needle syringe programs

Access to HCV treatment by PWID can be challenging due to multiple factors

Patient-related factors

Negative perceptions of HCV and treatment, Comparing to Peg-Riba

Overcoming challenges in the treatment of HCV in PWID

Dillon JF, et al. Hepatol Med Policy 2016;1:2

PRACTITIONER

Practitioner-related factors

Concerns relating to treatment

of a PWID population

-- Recent IVDU

-- Poor adherence

-- Early treatment discontinuation

-- Suboptimal SVR

-- Re-infection

System-related factors

▪Lack of treatment pathways adapted to treat PWID

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Integrated primary care community-based model: the potential to overcome barriers PWID have in accessing HCV care

Overcoming challenges in the treatment of HCV in PWID

Dillon JF, et al. Hepatol Med Policy 2016;1:2 PWID: people who inject drugs

Opioid substitution therapy (OST)

Needle/syringe programme

(NSP)

Psychological care and support

HIV testing and care

HCV screening

Peer support

Antiviral therapy

Harm reduction andcare support services

- Community-based- Comprehensive

If positive, assess for

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Fourth Objective




• Value of Cure



Individual and societal benefits of HCV cure

Value of HCV cure

. AASLD/IDSA Guidance. Available at: www.hcvguidelines.org (accessed August 2017); 2. Backus LI, et al. Clin Gastroenterol Hepatol 2011;9:509–16; 3. Leidner AJ, et al. Hepatology 2015;61:1860–9; 4. Gordon SC, et al. Hepatology 2012;56:1651–60

Individual benefits of HCV cure

•Prevents progression to cirrhosis and hepatocellular carcinoma1,2

•Reduces morbidity and mortality1

•Improves quality of life1

Societal benefits of HCV cure

▪Prevents onward transmission1

▪Reduces health service usage and costs1,3,4

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Increased SVR and treatment uptake could result in a substantial reduction in HCV-related morbidities

Modelling of number of events avoided as a result of HCV infections avoided*

Value of HCV cure

Bennett H, et al. PLoS ONE 2015;10:e125846*Based on a modelled population of 4,240 PWID and compared against baseline treatment uptake (8/1000 PWID.

CC: compensated cirrhosis; DC: decompensated cirrhosis; HCC: hepatocellular carcinoma; PWID: people who inject drugs; SVR: sustained virological response

Downstream cost savings are possible as a result of avoiding future complications of new chronic HCV infections

10/1000 PWID

20/1000 PWID

40/1000 PWID

80/1000 PWID

150/1000 PWID

250/1000 PWID

SVR 90%SVR 58%

CC DC HCC Transplant Death CC DC HCC Transplant Death

400

300

200

100

0

Tota

l eve

nts

avo

ided

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Fifth Objective




• Value of Cure



PWID populations included in clinical trials with DAAs

Treatment of HCV in PWID

Lalezari J, et al. J Hepatol 2015;63:364–9;Grebely J, et al. Clin Infect Dis 2016;63:1405–11; Grebely J, et al. Clin Infect Dis 2016;63:1479–81; Dore G, et al. Ann Intern Med 2016;165:625–34;Grebely J, et al. EASL 2017; Poster #FRI234 DAA: direct-acting antiviral agent; OST: opioid substitution therapy; PWID: people who inject drugs

Lifetime PWID

Ongoingdrug use

OST

OST and ongoingdrug use

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• PWID populations included in clinical trials with DAAs

– Patients on OST (Phase 2 AbbVie trial; ION-1, 2 and 3, ASTRAL-1, 2 and 3)

– Patients on stable OST, ongoing injection use permitted (C-EDGE CO-STAR)

– Patients on and not on OST with ongoing injection use (SIMPLIFY)

OST – Opioid

Substitution Therapy

Response rate by receipt of OST in the ASTRAL Phase 3 studies with 12 weeks’ SOF/VEL

Treatment of HCV in PWID

Adapted from Grebely J, et al. Clin Infect Dis 2016;63:1479–81 and supplementary appendix Error bars represent 95% CI.

OST: opioid substitution therapy; PWID: people who inject drugs; SOF: sofosbuvir; VEL: velpatasvir

Post-hoc analysis of data from ASTRAL-1, -2, -3 studies in patients on stable OST

194/198

12/12

116/117

1/1

230/230

7/8

241/253

23/24

110/110

6/6

966/984

49/51

SVR

12

(%

)

• No significant differences were identified between OST and non-OST participants:

– Overall SVR12 (96% vs 98%, P=0.26)

– Adherence ≥80% (90% vs 96%, P=0.06)

– Proportion with adverse events (86% vs 79%, P=0.29)

‡

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SOF-Based DAA Regimens in HCV GT 1-6 Patients Receiving OST

Grebely J, INHSU 2017; Poster #48

Sofosbuvir-based therapies are effective and safe in patients receiving stable OST during HCV therapy

CharacteristicOST

(n=194)No OST

(n=4549) P value

Adverse events, n (%) 151(78) 3502 (77) P=0.79

Serious adverse events, n (%)

7(3.6) 109 (2.4) P=0.24

Safety Results

SVR12 in OST Group:* by OST Type, Cirrhosis Status and GT 1a vs. GT 3 (Intention-to-Treat Analysis)

107113

7275

6970

114124

7074

8084

SVR

12

(%

)

P=0.68 P=0.089 P=0.850

*Pooled data across treatment regimens and durations

Analysis of Phase 3 ION, ASTRAL, and POLARIS Trials ‡

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Glecaprevir/Pibrentasvir in Treatment of Hep CA Real-Life Study (MISTRAL) in Italy

• Prospective 22-center study in 1,177 HCV-infected patients, of whom 118 (10%) were PWID.

• A higher percent of PWID had genotype 3 (33.9%) compared to non-substance users (7.9%).

• Overall SVR12 was 98.9%, with similar SVR12 in PWID vs non-PWID (98.3% vs 99.2%)

• Among PWID, SVR12 was 100% in geno 1a,1b, 2, 4, and 95% in geno 3 patients.

Persico M, et al., Liver Int. 2019 Jun 7. doi: 10.1111/liv.14170. [Epub ahead of print]

29

Efficacy of HCV DAAs in PWID and OST PatientsRe-Infection Rates

23 articles and conference presentations from 2010–2018

Graf, AASLD 2018, 640

Pooled SVR Between PWID and Controls

Pooled SVR Between OST Patients and Controls

HCV treatment outcomes in PWID and patients on OST are similar to those in the general HCV population

Re-infection rates:OST: 1.25% (10 out of 802 patients, 0-12.5/100 PY)

Systematic Review / Meta-Analysis ‡

Re-infection rates:PWID: 0.05% (1 out of 188 patients, 0-2.6/100 PY

PY = person-years

Sixth and Last Objective




• Value of Cure



WHO global health sector HCV strategy

Guidelines recommendations for managing HCV in PWID

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WHO global health sector strategy on viral hepatitis. Available at: http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf?ua=1 (accessed August 2017)

PWID: people who inject drugs; WHO: World Health Organization

90%

reduction in new

infections

90%

of HCV-infected people diagnosed

80%

of eligible patients treated

65%

reduction in mortality

100%Percentage of blood donations screened

300Number of sterile

needles/syringes provided per PWID/year

90%

Percentage injections administered with

safe devices

2030 targets for elimination of HCV as a public health threat

AASLD, IDSA Guidelines:Recommendations for Screening and Treatment of PWID

• Annual HCV-Ab testing of all PWID, more often depending upon the risk level

• Provide substance use disorder programs, needle-syringe exchange programs, offer routine opt-out HCV-Ab testing and reflex testing of HCV RNA for diagnosis of active infection, and if positive, offer linkage to care

• Counseling of PWID to reduce transmission to others

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

Thank you

Impact of Opioid Addiction on Hepatitis C Infection · Overall, individuals with HIV/HCV...

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