Treat To Prevent – Millennials, Drugs and Hepatitis C [HCV] - PowerPoint Presentation

Slide1

Treat To Prevent – Millennials, Drugs and Hepatitis C [HCV]Strategies To Identify and Advance PWID HCV Patient CareLinkage to C Care Program

Imtiaz Alam, M.D.

Medical Director, Austin Hepatitis Center

Medical Director,

HepCare

Specialty Pharmacy

Clinical Associate Professor of Medicine, Texas A & M University

HIV Outreach Workers & HIV Early Intervention Case Management ConferenceSlide2

When asked why he robbed banks Willie Sutton replied:“Because that is where the money is” Slide3

Over 5.2 Million People Living With Chronic HCV in the US

Number of HCV Cases (millions)

3.2

NHANES

Estimate

*Homeless (n=142,761-337,6100); incarcerated (n=372,754-664,826); veterans (n=1,237,461-2,452,006); active military (n=6805);

healthcare workers (n=64,809-259,234); nursing home residents (n=63,609); chronic hemodialysis (n=20,578); hemophiliacs

(n=12,971-17,000).

1.9

HCV Cases Not Included in NHANES*

Chak

E, et al. Liver Int. 2011; 31:1090-1101.

3.8

5.2

7.1

Conservative estimateUpper limit of estimate

Estimated

Total HCV CasesSlide4

Patients Should be Screened for HCV According to Birth Cohort and Risk Factors

1,2

Smith BD, et al.

MMWR Recomm Rep

. 2012;61:1-32.

Moyer VA; US Preventive Services Task Force.

Ann Intern Med. 2013;159:349-357.Persons Born Between1945 and 19651,2The 1945-1965 birth cohort was selected on the basis of HCV prevalence and disease burden

One-time screening for HCV infection in the birth cohort may identify infected patients at earlier stages of disease Birth Cohort ScreeningRisk Factor–Based Screening

Past or current injection drug useReceiving a blood transfusion before 1992Long-term hemodialysisBeing born to an HCV-infected motherIncarcerationIntranasal drug useGetting an unregulated tattooOther percutaneous exposures

Important Risk Factors1,2

Patient Screening for HCVSlide5

Hepatitis C is an INFECTIOUS

Virus

Treatment as Prevention

Slide credit:

clinicaloptions.com

1. Terrault NA, et al. Hepatology. 2013;57:881-899. 2. Thomas SL, et al. Int J Epidemiol. 1998;27:108-117. 3. Larsen C, et al. PLoS One. 2011;6:1-9. 4. Shepard CW, et al. Lancet Infect Dis. 2005;5:558-567.

Infection in monogamous heterosexual couples is rare

[1]

Risk of transmission from mother

to child is low

[2]

Sex between men who are HIV-positive increases the risk of contracting

HCV

[3]

People who

inject drugs

account for the majority of new cases of HCV in developed countries

[4]Slide6

What Does the Term “PWIDs” Refer to?

“PWIDs” is a subjective term referring to any people who have ever injected drugs

1

Once

Regularly

OccasionallyNo longer (ie, on stable OST)Previously (eg, ever in the past)PWID populations1,2:“Active” or “recent” PWIDs – injected drugs within 1 month to 1 year* and are at risk for transmitting/acquiring HCV infection“Former” PWIDs – ceased injecting drugs but may have existing HCV infection

*There are varying definitions in literature.1. Larney S, et al. Int J Drug Policy. 2015;26(10):950-957. 2. Grebely J, et al. Int

J Drug Policy. 2015;26(10):1028-1038. 3. Moyer VA. Ann Intern Med. 2013;159(5):349-357. NSP, needle/syringe program;OST, opioid substitution therapy.

Due to the relapsing nature ofdrug dependence, active PWIDsoften move between populationsand may access harm reductionservices at any time.1

Lifetime PWIDsActive PWIDs

OSTNSPPast or current injection drug use is the most important risk factor for HCV infection.3 − US Preventive Services Task ForceSlide7

Fixed

Detachable

Zibbell

J, CDC,

Presented

as part of Hepatitis C Prevention Opportunities Among PWID, April 28, 2015. Transmission Via Contact with Contaminated Blood: Needles and SyringesSlide8

Filters

Cookers

Water

Surfaces

Zibbell

J, CDC,

Presented as part of Hepatitis C Prevention Opportunities Among PWID, April 28, 2015. Transmission Via Contact with Contaminated Blood: Preparation EquipmentSlide9

Fingers on cooker and in solution

Bloody fingers

Zibbell

J, CDC,

Presented

as part of Hepatitis C Prevention Opportunities Among PWID, April 28, 2015. HCV TransmissionSlide10

HCV-contaminated solution needs to be heated for almost

90 seconds

and reach temperatures of

144°F

for the virus to be at undetectable levels.

Paintsil, et al. JID. 2010; Doerrbecker, et al. JID. 2011; Thibault, et al. JID. 2011; Doerrbecker, et al. JID. 2012; Paintsil, et al. JID. 2014.How Long Can HCV Survive onInanimate Objects?Slide11

IDU Is the Most Important Risk Factor for HCV Infection Globally

In most developed countries, IDU increased in the 1970s and 1980s and is

now the main risk factor for HCV infection in these countries

1

*Data identified in a systematic literature search (up until May 2011) with wider input from relevant organizations; Regional data are PWIDs positive for HCV antibodies (midpoint estimates).

1. Midgard H, et al.

J

Hepatol. 2016;65(Suppl 1):S33-S45. 2. Grebely J, Dore GJ. Antiviral Res. 2014;104:62-72.

IDU, injection drug use.Anti-HCV Prevalence Among PWIDs (million)

1,2,*No evidence of IDU

No eligible report (74 countries)<40% (16 countries)

40%-<60% (24 countries)60%-<80% (25 countries)≥80% (12 countries)

Prevalence of HCV in PWIDsSlide12

1. Grebely J, et al.

Int J Drug Policy

. 2015;26(10):1028-1038. 2.

Grebely J, et al.

Clin Infect Dis

. 2013;57(7):1014-1020.

Globally, Approximately Two-thirds of PWIDs Have HCV67

%OF TOTAL PWIDs1…that is

~80%

of new HCV infections resultfrom IDU2

MILLION PWIDs

have HCV…110Slide13

*Estimated prevalence of acute HCV infections after adjusting for under-ascertainment and under-reporting. Latest available data.

1. Campbell CA, et al.

MMWR Morb Mortal Wkly Rep

. 2017;66(18):465-469. 2. CDC. Hepatitis Surveillance Report – United States. https://www.cdc.gov/hepatitis/statistics/2015surveillance/commentary.htm. Accessed May 11, 2017. 3. Litwin AH, et al.

Clin Infect Dis

. 2005;40(Suppl 5):S339-S345. 4. CDC. Hepatitis Surveillance Report – United States. https://www.cdc.gov/nchhstp/newsroom/2017/hepatitis-surveillance-report.html. Accessed May 11, 2017. IDU Is the Primary Risk Factor for New HCV Infections in the United States1

~3.5 million people

living with chronic HCV in the United States2

are current or former PWIDs3~60%With an estimated 34,000 new HCV infections in the United States in 2015,

new infections have nearly tripled in the past 5 years, reaching a 15-year high.2,4,* The greatest increases in new HCV infections, and the highest overall number of cases, were among young people aged 20-29 years, with injection drug use as the primary route of transmission.4Slide14

HCV Infection Incidence Rates Increasing in IDU and MSM

Wandeler

G et al.,

CID

2012: Nov 15; 55(10): 1408-16Slide15

Increased Prevalence in HIV [-] MSM in PrEP Program

Sexually transmitted HCV – HIV [+] MSM > HIV [-] MSM

Recent studies have shown increased prevalence among HIV [-] MSM

Kaiser Permanente San Francisco

PrEP

ProgramU.K. PROUDFrench Ipergay PrEP StudyCROI 2017 - Amsterdam Pre-Exposure Prophylaxis Project (AMPrEP):4.8%, tested positive for either HCV antibodies or HCV RNA at baseline [n=18]25% of MSM HCV Ab [+] (4 out of 18) reported injecting drugs during the 3 months before starting PrEP -- much higher than the 3% (11 out of 357) among HCV Ab [-] participantsMSM HCV Ab [+]:were younger on average than those without HCV (median 33 vs 40 years)had more anal sex partners (median 20 vs 15)were more like to have been recently diagnosed with chlamydia, gonorrhea, or syphilis (61% vs 35% in the past 6 months)engaged in "chemsex," or use of certain recreational drugs during sex (83% vs 40% in the past 3 months)Routine testing for HCV in

PrEP ProgramsSlide16

Past Year Heroin Initiates Among People Aged ≥12 Years, by Age Group (in Thousands): 2002-2015*

2002

2003

2004

2005

2006

2007

2008

200920102011

20122013

20142015

12 or older

18 to 25

12 to 17

26 or older

Year

Past Year Initiates

(in thousands)

NSDUH Shows Increasing Trend in Heroin Use Among Youth

*Caution is advised in interpreting the fluctuations in the numbers of heroin initiates in single years because the relatively small numbers of respondents aged ≥26 years who reported that they initiated heroin use in the past year can greatly influence estimates of initiates aged ≥26 years in a single year; these respondents aged ≥26 years often represent large numbers of people in that age group.

Lipari R, et al. 2015 NSDUH Survey. 2016;1-34.

NSDUH, National Survey on Drug Use and Health.

“+” = Difference between this estimate and the 2015 estimate is statistically significant at the 0.05 level.

The average age at first heroin use is 25.4 years.

Heroin use has

doubled among people aged ≥26 years

in the past decade

In 2015, there were

136,000 new initiates

of heroin use

11,000 adolescents (aged 12-17 years)

57,000 young adults (aged 18-25 years)

68,000 adults (aged ≥26 years)Slide17

A Surge in Heroin Injection Drug Use is Shifting the Epidemiology of HCVSlide18

Hepatitis C Infections Soaring

Fueled by Prescription Painkiller Abuse

CDC May 11

th

2017

2006-2012

Acute HCV infections x3 – age <30 yearsKY, TN, Virginia and WVNew HCV cases 1.25 per 100,000 [2006] vs. 4 per 100,000 [2015]2013 – KY – 5.1 cases per 100,0002013 – DE & SC – NO reported cases First time heroin users90,000 [2006] vs. 156,000 [2012]Slide19

Increased IDU in Adolescents and Young Adults Is Shifting the Demographics of HCV Infection in the United States

*Excludes 35 cases with missing age or sex information.

†

Excludes 346 cases with missing age or sex information.

‡

Among persons aged 15–24 years.CDC. MMWR Morb Mortal Wkly Rep. 2011;60(17):537-541.

5

4

3

2

0

1

10

20

30

40

50

60

70

80

90

Age (years)

Percentage

of Total Cases Reported for the Year

Male

Female

2002

5

4

3

2

0

1

10

20

30

40

50

60

70

80

90

Age (years)

2009

Newly Reported Confirmed HCV Cases,

Massachusetts, 2002-2009

N=6281*

N=3904

†

Male

Female

IDU was the most common risk factor for HCV transmission

‡

Increased IDU is not unique to Massachusetts; these data may be indicative of emerging trends in HCV transmission in other regions of the United States.Slide20

HCV Outbreaks Associated With IDU Are

Occurring Throughout the United States

CDC, Centers for Disease Control and Prevention.Slide21

Injection Networks Are Driving Hepatitis C Outbreaks

*Based on data from national surveillance and supplemental case follow-up at selected jurisdictions describing the US epidemiology of HCV infection among young persons (aged ≤30 years).

Suryaprasad AG, et al

.

Clin Infect Dis

. 2014;59(10):1411-1419.

Higher incidence of HCV infection (especially among younger PWIDs) in 2012 than in 2006 in at least 30 states, with the largest increases occurring in nonurban counties east of the Mississippi River*Data indicate an emerging US epidemic of HCV infection among young nonurban persons (aged ≤30 years).Slide22

“ It is estimated that within the first 5 years of injection practices, about 50% of the people who inject drugs will become infected by HCV”Julie Bruneau

, MD

Professor of Family Medicine, University of MontrealSlide23

“Currently only 1-2% of People Who Inject Drugs [PWID] with chronic HCV infection are treated each year”!!Holly Hagan, PhDProfessor NYU College of NursingSlide24

HCV disproportionately impacts PWIDs, but treatment rates are even lower relative to the overall HCV population

5

0%

HCV Is Underdiagnosed and Undertreated,

Even More for PWIDs

Cascade of Care*

*All numbers are approximate.

†

2003-2013.

‡Estimated, 2005. §Estimated, 2014.1. Yehia BR, et al. PLoS One. 2014;9(7):e101554. 2. Litwin AH, et al.

Clin Infect Dis. 2005;40(Suppl 5):S339-S345. 3. Coffin PO, Reynolds A. Hepat Med. 2014;6:79-87.

Chronic HCV infection

Diagnosed and aware

Treated

HCV in general US population

HCV in PWID US population

16%

~1.75 Million

1,†

~560,000

1,†

1%-9%

~3.5

Million

1,†

~2.1

Million

2,‡

~1 Million

3,

§

≤~189,000

3,§

49%Slide25

REASON

1-3

?

Perceived Barriers to HCV Care in the PWID Population

*Individuals born between 1945-1965 were screened for HCV through a testing and linkage-to-care program in 2 community clinics in Denver, Colorado. HCV evaluation and treatment courses were followed prospectively from January 2013–March 2015.

1. Asher AK, et al.

Subst Use Misuse. 2016;51(9):1218-1223. 2. Rich ZC, et al. BMC Public Health. 2016;16:994-1003. 3. Aspinall EJ, et al. Clin Infect Dis. 2013;57(Suppl 2):S80-S89.4. Muething L, et al. IDSA/ID Week 2015. Poster 1029.

In a single-center study in Denver, Colorado, individuals (born 1945-1965) with substance abuse were less likely to be referred compared with those without substance abuse, but if referred were equally likely to attend an HCV specialty visit (n=250)4,*

Mental illness

Substanceabuse

Reinfection

AdherenceSlide26

Barriers to Care Identified by Pts in OST Clinics and Needle Exchange Programs

Survey of PWID in Philadelphia needle exchange program (N = 188)

Fear of

Judgement

by Doctor

0

20

40

6080100

NoInsuranceCan’t AffordCopay

Can’t AffordTransport

Treatment Will MakeMe SickFear ofLiver Biopsy

Feel FineWithoutTreatment

Pts (%)

Self-Reported Barriers to Care Among HCV-Infected PWID (n = 117)

Slide credit:

clinicaloptions.com

Feller SC, et al. AASLD 2013. Abstract 274.Slide27

1.

AASLD/IDSA HCV Guidance. www.hcvguidelines.org/full-report-view. Accessed April 23, 2017.

2.

European Association for Study of Liver.

J Hepatol

. 2017;66(1):153-194.3. WHO guidelines approved by the guidelines review committee. Geneva: World Health Organization. 2016. 4. Grebely J, et al.

Int J Drug Policy. 2015;26(10):1028-1038.Major Global Organizations Recommend HCV Treatment for PWIDs1-4PWIDs HCV MANAGEMENT

AASLD/IDSAAmerican Association for the Study of Liver Diseases/Infectious DiseasesSociety of America

WHOWorld Health Organization

EASLEuropean Association for the Study of the LiverINHSUInternational Network for Hepatitis in Substance UsersSlide28

Chronic HCV Infection Can Result in Cirrhosis and Can Increase the Risk for Hepatocellular Carcinoma (HCC)* if Not Treated

*All percentages are approximate.

†

20%-30% of individuals are symptomatic.

Adapted from Chen SL, Morgan TR.

Int J Med Sci

. 2006;3(2):47-52.

RNA, ribonucleic acid.

HCC per year1%-4%Decompensated cirrhosisUp to 30% at 10 years

Clearance of

HCV RNA15%-25%Potential extrahepatic manifestations

Acute infection†

Chronic infection75%-85%

Cirrhosis (within the first 20 years)10%-20%Slide29

Ascites: Most Common Complication

of Cirrhosis

Estimated that 10 years after a diagnosis of compensated cirrhosis 50-70% will develop ascitesSlide30

Factors Associated With Accelerated Fibrosis Progression

Host

Viral

Modifiable

Alcohol consumption

Nonalcoholic fatty liver disease

Obesity

Insulin resistanceNon-modifiableFibrosis stageInflammation gradeOlder age at time of infectionMale sexOrgan transplant

Genotype 3

Coinfection with HBV or HIVAASLD, IDSA, IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed July 15, 2015.Slide31

More People Die From HCV Than Other Infectious Diseases

(Including HIV)

*Extended from: Ly KN et al.

Ann Intern Med

. 2012;156(4):271-278.

†Including HIV, pneumococcal disease, and tuberculosis.1. Ly KN, et al. Ann Intern Med. 2012;156(4):271-278. 2. Holmberg S, Ly KN, Xing J, Moorman AC. Rising mortality from hepatitis C virus in the United States, 2002-2013.

Paper presented at: American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course; October 16-21, 2015; Honolulu, HI. 3. Ly KN, et al. Clin Infect Dis. 2016;62(10):1287-1288. 4. CDC. Annual number of HCV related deaths vs. other nationally notifiable infectious conditions in the United States, 2003-2013. 5. Smith BD, et al. MMWR Recomm Rep. 2012;61(RR-4):1-32.

The HCV mortality rate surpassed that ofHIV in 2007 and continued to rise1,2,*

More people die from HCV than from 60 other infectious diseases combined

2-4,†In 2007, patients with HCV died at a median age of 57 years. This is 20 years shorter than the average US lifespan.5

Annual number of HCV-related deaths vs other nationally notifiable infectious conditions in the United States, 2003-2013Slide32

1

2

5

4

3

6

3

HCV Has an Impact Beyond the Liver

1,2

*Secondary to mixed cryoglobulinemia vasculitis.

1. AASLD/IDSA HCV Guidance. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed April 23, 2017. 2. Jacobson IM, et al.

Clin Gastroenterol Hepatol

. 2010;8(12):1017-1029.

1

2

3

4

5

6

Strongly Associated Extrahepatic Manifestations

Mixed cryoglobulinemia vasculitis

Lymphoproliferative disorders

Peripheral neuropathy*

Membranoproliferative glomerulonephritis*

Insulin resistance

Cutaneous manifestations (eg,

lichen planus, porphyria cutanea tarda, palpable purpura*

)Slide33

9

1

2

5

4

3

6

7

10

11

8

HCV Infection Increases the Risk for Depression, Diabetes,

and Other Conditions

1-14

*Secondary to mixed cryoglobulinemia vasculitis.†Conflicting or equivocal data from studies.1. Adinolfi LE, et al. World J Gastroenterol. 2015;21(8):2269-2280. 2. Younossi ZM, et al. Aliment Pharmacol Ther. 2013;37(6):647-652. 3. Younossi

ZM, et al. Aliment Pharmacol Ther. 2014;39(5):518-531. 4. Park H, et al. J Viral Hepat. 2015;22(11):897-905. 5. Molnar MZ, et al. Hepatology. 2015;61(5):1495-1502. 6. Gonzalez HC, et al. Dig Dis Sci. 2015;60(6):1820-1824. 7. Huang H, et al. PLoS One. 2013;8(11):e81305. 8. Huang H, et al. PLoS One. 2014;9(9):e106376. 9. Thames AD, et al. Neurol Neuroimmunol Neuroinflamm. 2015;2(1):e59. 10. Wong RJ, et al. Dig Dis Sci. 2014;59(7):1586-1593. 11. Pothineni NV, et al. Am J Cardiol. 2014;114(12):1841-1845. 12. Lai JC, et al. Dig Dis Sci. 2015;60(6):1813-1819.

13. White DL, et al. J Hepatol. 2008;49(5):831-844. 14. Clifford DB, et al. Neurology. 2015;84(3):241-250.

Possibly Associated Extrahepatic Conditions

INCREASED RISK FOR

Depression

Carotid atherosclerosis/atherothrombosis

Type 2 diabetes mellitus

Hypertension

Congestive heart failure

Chronic kidney disease

End-stage renal disease

Kidney cancer

Other renal manifestations (eg

, glomerulonephritis, proteinuria

)*

Low bone mineral density

Rheumatologic manifestations (eg

, polyarthralgia, polyarthritis

)

*

Fatigue

2

1

3

4

5

6

7

8

9

POSSIBLE INCREASED RISK FOR

†

Neurologic impairment/disorders

Stroke

Coronary artery disease/ischemic

heart disease

10

11Slide34

The possibility of eliminating the virus and achieving a cure may be due to the manner in which the virus infects the host cells

1

HCV does not integrate into the nuclei of infected cells, whereas HBV and HIV DNA are incorporated into the nucleus of the cell

1

*HBV cccDNA: accumulates in hepatocyte nuclei, acting as a template for viral messenger RNA transcription.

†

HIV proviral DNA: integrates into the chromatin of infected cells, acting as the template for the transcription of viral genes.

‡Including diabetes, hypertension, and hyperlipidemia.1. Soriano V, et al. J Antimicrob Chemother. 2008;62(1):1-4. 2. Last AR, et al. Am Fam Physician. 2011;84(5):551-558. 3. World Health Organization. Advocacy Brief. May 2016. 4. AASLD/IDSA HCV Guidance. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed April 23, 2017.

cccDNA, covalently closed circular DNA; DNA, deoxyribonucleic acid.HCV1

HBV1HIV1

Unlike Some Chronic Conditions, HCV Can Be Cured

Although other chronic conditions‡ require lifelong management, HCV is curable, with an average treatment duration of 12 weeks with highly effectiveall-oral treatments.1-4Slide35

Benefits of Achieving SVR

↓

Cirrhosis

↓

Decompensation

↓ HCC↓ Transplantation↓ All-cause mortalityImproved QoLMalignancyDiabetesCVDRenal

NeurocognitiveCure

Improved clinical outcomes[1,2]

Slide credit:

clinicaloptions.com

1. Smith-Palmer J, et al. BMC Infect Dis. 2015;15:19.2. Negro F, et al. Gastroenterology. 2015;149:1345-1360.3. George SL, et al. Hepatology. 2009;49:729-738.

HepaticExtrahepatic

Decreased transmission[1]Slide36

Treatment for HCV Has Evolved

Before 2011, HCV treatment could last as long as a year, with cure rates* (SVR) of 40%-50% for the most common genotype in the

United States

1

Since that time, scientific advances have made HCV treatment shorter (as few as 12 weeks) and more effective

2

Interferon-free treatment options are available that have shown cure rates of approximately 95% in clinical studies2,3,*

*Cure, also known as SVR, is defined as no detectable HCV in the blood at least 12 weeks after completion of therapy.1. Ghany MG, et al. Hepatology. 2011;54(4):1433-1444. 2. AASLD/IDSA HCV Guidance. Recommendations for testing, managing, and treating hepatitis C. http:/www.hcvguidelines.org. Accessed April 23, 2017. 3. US DHHS, Center for Drug Evaluation and Research. Draft Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment. May 2016.

Direct-Acting

Antiviral Era

Cure rates: ~95%

Interferon Era

Cure rates: 40%-50%Slide37

IFN-Free DAA Therapy: OST vs Non-OST in Phase II/III Trials

Slide credit:

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1. Feld JJ, et al. N Engl J Med. 2014;370:1594-1603. 2. Puoti M, et al. AASLD 2014. Abstract 1938. 3. Lalezari J, et al. J Hepatol. 2015;63:364-369. 4. Grebely J, et al. Clin Infect Dis. 2016;[Epub ahead of print]. 5. Grebely J, et al. Clin Infect Dis. 2016;[Epub ahead of print]. 6. Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.

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

n/N =

0

60

80

40

20

100

49/

51

966/

984

98

96

455/

473

54/

56

37/

38

269/

296

299/

316

66/

70

1822/

1882

OBV/PTV/RTV + DSV + RBV

[1,2]

96

97

95

91

SVR12 (%)

97

96

94

OBV/PTV/RTV + DSV + RBV

[3]

LDV/SOF

+ RBV

[4]

SOF/VEL

[5]

EBR/GZR

[6,7]

No OST

OSTSlide38

Active

Injectors

Opioid

Agonist

Therapy

Former

Injectors

PWIDs Across the Spectrum Can Be Treated for HCV

*Studies utilized IFN/RBV as the treatment arm.

1. Robaeys G, et al. Clin Infect Dis. 2013;57(Suppl 2):s129-s137. 2. Dimova RB, et al. Clin Infect Dis. 2013;56(6):806-816. 3. Zeremski M, et al. World J Gastroenterol. 2013;19(44):7846-7851.

IFN, interferon. Among patients on opioid agonist therapy, HCV treatment outcomes improved among those treated for opioid addiction compared with nonaddiction-treated drug users2,*

Among active injectors, frequent drug use (daily/every other day) has an impact on adherence, treatment completion, or treatment efficacy; occasional drug use does not1,*Among former injectors, successful HCV outcomes are more likely to be achieved if PWIDs are stabilized for addiction and then undergo HCV therapy3,*Slide39

IFN Era: Adherence Among PWIDs Has Historically Been Comparable to the Overall HCV Population (2001-2007)

1

1. Hellard M, et al.

Clin Infect Dis

. 2009;49:561-573. 2. Litwin A, et al. INHSU 2016. Oral presentation.

Non-PWIDs who

initiated treatment

79%completed treatment

PWIDs who initiated treatment

71%completed treatment(N=655)Adherence in PWIDs has been shown to be similar

using newer IFN-free regimens.2(N=844)Slide40

Reinfection Is Rare, Even Among High-Risk Groups

A global meta-analysis of 14 articles that assessed HCV recurrence in high-risk patients; 12 evaluated the risk in PWIDs*

*

Studies included adults (aged ≥18 years) who achieved SVR12 or SVR24 post-treatment with IFN-based therapies.

†

Includes 2 studies conducted in prisons and was not specific to PWIDs.

Simmons B, et al.

Clin Infect Dis. 2016;62(6):683-694.

PYFU, person-years of follow-up.Re-infections/1000 PYFU

North American StudiesEuropean StudiesTotal PWIDs 15 20 23 35 15 9 8 61 42 27 277 20 617

studied Re-infections 1 2 1 2 1 1 2 5 1 1 7 0 27 TOTAL

North American and European Reinfection Rates for PWIDsReinfection rate among high-risk populations (PWIDs and Prisons)19.06/1000 PYFU†Slide41

HCV Reinfection Over 5 Yrs by Study Population

Slide credit:

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Simmons B, et al. Clin Infect Dis. 2016:62:683-694.

43 studies (n = 7969;

avg. FU: 3.9 yrs)

14 studies (n = 771;

avg. FU: 2.8 yrs)

4 studies (n = 309;

avg. FU: 3.3 yrs)

0

10

6

2

16

Low Risk

1

HCV Recurrence at 5 Yrs (%)

10

8

12

4

14

PWID/Prisoner

HIV Coinfected

15Slide42

Specific Issues Related to HCV Reinfection

Acknowledgement:

There will be cases of HCV reinfection

Harm reduction access (NEP, OST):

To reduce risk of reinfection

Individual-level strategies:

Treatment of injecting partnersRapid scale-up: Initial increase in reinfections, then controlAccess to retreatment: Without stigma and discrimination

Slide credit:

clinicaloptions.comSlide43

Pts With Minimal Liver Disease Denied HCV Treatment Access in Many Settings

Medicaid reimbursement criteria for DAAs based on documented liver fibrosis stage required for reimbursement

Slide credit:

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Greenwald R, et al. AASLD 2016. http://www.chlpi.org/stateofhepc.Slide44

HCV Cure Associated With Improved 15-Yr Survival in Pts With F0/F1 Disease

Single-center cohort of consecutive pts since 1992 (N = 1381)

Progression to F3/F4 was observed in 15.3% of F0/F1 pts with available liver biopsy (n = 157)

Slide credit:

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Jézéquel C, et al. EASL 2015. Abstract P0709.

1.0

0.8

0.6

0.4

0.2

00

510

1520Yrs From Biopsy to Death

F0/F1 FibrosisP = .003Treated pts without SVRUntreated ptsTreated pts with SVR

SurvivalSlide45

Substance abuse treatmentHARM ReductionHCV Testing

Linkage to HCV Care

Monitoring Adherence to HCV Therapy

Post-therapy Cure Surveillance – Prevent Re-infection

“Treat to Prevent”

“One-Stop” ShoppingCollaborative Care ModelSlide46

Screening and Linkage to Care Can Help Lead to Curing HCV for Our HCV-Positive PWID Patients

Screen

High-risk patients should be screened whether

or not symptoms are present

Refer Patients to HCV Care

Assist with

scheduling the appointment

Follow Up With Patients and HCV Care Provider

Call to check

that your patient followed through

Diagnose

Explain to your patient what a diagnosis of HCV means and that HCV is curableSlide47

1. Beirness DJ, et al. Canadian Centre on Substance Abuse. 2008. 2. Logan DE, Marlatt GA.

J Clin Psychol

. 2010:66(2):201-214.

Harm Reduction Facilities Use By PWIDs Can Increase Adoption of Lower-risk Alternative Injection Practices

1

Needle- Exchange Programs

1

Opioid Substitution Therapy1

Risk Counseling2

Street/Peer Outreach Programs1

Supervised InjectionSites1Slide48

Comprehensiveness of State Laws Pertinent to Prevention of HCV Infection Among PWIDs*

Assessment of whether a state had established

Authorization of syringe exchange statewide or in selected jurisdictions

Exemption of needles or syringes from the definition of drug paraphernalia

Decriminalization of possession and distribution of syringes or needles for participants of a legally authorized syringe service program

Avoidance of criminal prosecution for possession of drug paraphernalia by disclosing possession of a needle or sharp object to an arresting officer

Allowance for the retail sale of syringes without a prescription to PWIDs

*United States, 2016.Campbell CA, et al. MMWR Morb Mortal Wkly Rep. 2017;66(18):465-469.

Most comprehensive

More comprehensiveModerateLess comprehensiveLeast comprehensiveSlide49

You Are the First Line of Communication

for Patients With Addiction

Give your patients a chance to be cured with 3 simple steps.

*Screening for HCV antibodies does not have to be with a blood test. It can be via oral swab, or an even simpler approach, asking the patient questions about injecting drugs even once then proceed to the blood test for HCV RNA.

Test at-risk patients with a blood test to detect the presence of HCV antibodies*

Screen for HCV antibodies

A blood test for the presence of HCV RNA will confirm an HCV diagnosis in patients who test positive for HCV antibodies

Diagnose with an HCV RNA test

Refer your patients with HCV to an experienced HCV clinician for treatment evaluation, regardless of symptoms

Refer to an experienced HCV clinicianSlide50

Cascade of Care for Suburban Heroin Users 17-35 years age, New Jersey Oct 2014-June 2015

N = 861 were HCV Ab tested

N = 16 patients returned for in-office F/U visits

N = 2 started treatment

Akyar

E et al. Emerg Infect Dis; 22 [5]; May 2016Slide51

Various Clinical Models Have Demonstrated Improved Linkages to HCV Care for PWIDs

AASLD/IDSA. Recommendations for Testing, Managing, and Treating Hepatitis C. http://www.hcvguidelines.org. Accessed August 18, 2015.

University of New Mexico. Project ECHO Model. http://echo.unm.edu/about-echo/model/. Accessed August 18, 2015.

Arora S, et al.

N Engl J Med

. 2011;364:2199-2207.

Rossaro L, et al. Dig Dis Sci. 2013;58:3620-3625.

“Evaluation by a practitioner who is prepared to provide comprehensive management, including consideration of antiviral therapy, is recommended for all persons with current (active) HCV infection.”— AASLD/IDSA Recommendations for Testing, Managing, and Treating Hepatitis C1

Colocated or Integrated Care

Designed to impact loss to follow-up1Potentially affects access to treatment1

Telehealth

Delivers service to underserved populations

2

Links specialists to communities2Has shown similar safety and efficacy to non-telehealth settings for HCV patients3,4

Referral

Referral for HCV infection to an experienced HCV clinician

1

Multidisciplinary approach to treatment has the potential to mitigate barriers to HCV care

1Slide52

Prevent new infections

[HARM REDUCTION]

Detect and care for existing infections

[LINKAGE TO C CARE]

Reduce chronic infections

[TREAT TO PREVENT]

HCV Prevention Activities

Access to syringes & other equipmentOpioid Substitution Treatment [OST] – Buprenorphine/MethadoneSafe injection educationOutreach to those not engagedShort & Long Term Residential Treatment CentersOutpatient - Sober Living Homes

Screening and DiagnosisAntibody screeningHCV RNA test toconfirm infectionClinical evaluation to determine disease stageMonitoring disease progressionReduce alcohol useHCV care and TreatmentTreat to cure infection [DAA’s Rx] – Pharmacy

Mobile Medical ProviderTelemedicine – Project ECHO HCVSupport adherenceto treatment & evaluate PRO’s [Patient Related Outcomes]Support post-cure to prevent reinfectionCo-locating these services increases their impact on HCV control

Framework of a Model HCV Control Strategy For PWID“Treat to Prevent” Collaborative Care ModelSlide53

What Are The Barriers To HCV Linkage To Care?

Fragmentation of HCV services

Denial or lack of understanding about the importance of care

Concerns about costs of care

Conditions that make it harder for patients to enter care, like substance abuse and mental health issues

Difficulties arranging transportation, childcare, time away from work, or other logistics related to keeping appointments

Fear of stigmaSlide54

Goals of linkage to C care

Identifying persons infected with HCV early in the course of their disease

Earlier diagnosis and improvements along the entire continuum of care can lead to reductions in the incidence of cirrhosis, liver cancer and liver transplantations

Link and refer persons infected with HCV to care and treatment

List of medical providers treating HCV in every state

Improve access to and quality of care for persons with HCVDevelop networks to support specialty providers who are uniquely positioned and equipped to treat HCV – resulting in expanded capacity for HCV services across several systems Achieve “Real World” SVR >90% for ALL infected with HCVAdvance research to enhance care and treatment of persons infected with HCVResearch and analyses that describe the continuum of care in various settings can illuminate health disparities and guide resource allocation, program planning, and implementation Reduce overall cost of achieving HCV cureReduce stigma of treating PWID [People Who Inject Drugs] HCV patients Slide55

Linkage to C Carewww.linkagetocare.comHub and Spoke Model – Centralizes Multi-Site Communication

PWID HCV PATIENT IDENTIFIED

Patient Information Sent to Linkage to Care Program

Web-Based Program

[HIPPA Compliant]

Linkage to Care Specialist/Navigator

Community ClinicProject ECHO HCVUninsuredPatient

Local Private ProviderNetworkGI/HepatologyAddiction MedicinePrimary CareInsuredPatient

HARM ReductionAdherence To Clinical ProgramPost Therapy IDU Relapse & HCV Reinfection

HCV Antibody [Phlebotomy or OraSure] HCV RNA PCR QUANT & GENOTYPE Slide56

www.linkagetocare.comSlide57

https://youtu.be/i3Ruycukn60Slide58

What is Linkage To C Care?

Linkage to C care is a web based platform that assists people with HCV to enter into HCV medical care. Newly HCV-diagnosed persons need to connect quickly with a HCV provider and remain in care

Why Enroll In It?

Increases likelihood of newly HCV-diagnosed people accessing HCV treatment and remaining in HCV care

What Are The Benefits?

Provides patients the opportunity to get cured of HCV, thereby experiencing better health outcomes and significantly reduce the risk of transmitting HCVSlide59

Linkage to Care ReferralsSlide60

Users - MTD

21

Users - YTD

71

Users - Start

82

Counselors - MTD7Counselors - YTD

26Counselors - Start48Referrals - MTD59

Referrals - YTD166Referrals - Start207Questions - MTD

2Questions - YTD4Questions - Start

7Logins - MTD411Logins - YTD1015

Logins - Start1767Appt Sch - MTD26

Appt Sch - YTD50Appt Sch - Start60

Telemed - MTD2Telemed - YTD9

Telemed - Start9Link2Lab - MTD1Link2Lab - YTD

3Link2Lab - Start3Avg Response (Hours) - MTD

75

Avg Response (Hours) - YTD64

Avg

Response (Hours) - Start

84

Linkage to C Care March 2017 StatsSlide61

Linkage to c care program [LTC]

Jan – May 2017

289 HCV RNA [+] patients referred

31% self-referred

69% referred from 24 facilities in 15 states

66% uninsured

Median age 41 years [19-77]58% males70% Sober Living Homes 85% [n=246] were contacted by LTC specialist [LTCS]70% [n=173] were referred to a medical provider49% [n=120] HCV patients made it to first appointment 25% [n=30] HCV patients initiated DAA therapy30% [n=9] finished HCV DAA therapy71% seen in office vs. 14% telemedicine vs. 15% by telephoneMajority contacted within 2 days by LTCSINHSU September 2017Slide62

Treat to Prevent: Strategies To Identify and Advance PWID HCV Patient Care

62

PATIENT IDENTIFICATION

MEDICAL PROVIDER

REFERRAL

MANAGEMENT

Outreach & Awareness: First Contact:Recovery Treatment Center – Short & Long Term Residential Treatment Centers Sober Living Homes

Diagnosis: HCV Testing - AntibodyHCV Confirmation – PCR RNA QuantificationHCV GenotypingFibrosis Determination - FibroScanUrine Drug Toxicology TestingHAV and HBV Testing – VaccinationLiver Cancer Screening – Abdominal U/S

Clinical Care Coordination:Appropriate link to quality care – “Linkage To C Care”Care Specialist/NavigatorResearch SpecialistWebsite Portal - To submit and communicate information Improved information sharing & communication between treatment center & medical providerHCV Therapy:Medication – PharmacyCare – Face-to-Face [Mobile Provider or in office] +/- TelemedicineSupport Adherence to therapy

Monitor Patient Related Outcome to TherapyPrevent Post-Cure ReinfectionHARM Reduction:Opioid substitution therapy [OST] – Buprenorphine/MethadoneNeedle Exchange ProgramsBehavioral Health TherapyRelapse Prevention – Naltrexone

Integrated and Sustainable Care of PWID HCVSlide63

Global Call for HCV Elimination

Vision: “

A world where viral hepatitis transmission is stopped and everyone has access to safe, affordable, and effective treatment and care

”

2020 target: 3 million HCV infections treated

Feasible

by scaling up 6 key interventions to high coverage:Hepatitis B vaccination (including birth dose)Safe injection practices and safe bloodHarm reduction for injecting drug usersSafer sex (including condom promotion)Hepatitis B treatment Hepatitis C cure

Slide credit:

clinicaloptions.com

WHO. Towards the elimination of hepatitis B and C by 2030.

Draft WHO Global Hepatitis Strategy, 2016-2021.

2030 Targets

90% Diagnosed 80% Treated65% Reduced MortalitySlide64

ERADICATING HCV

Is

Everyone’s

Job in the Community

Identify undiagnosed HCV

HCV rapid testing

PWID – “Next Wave”Age cohortPreventing infection and reinfectionOutreach and educationSafer injection counselingReinfection prevention counseling

Treatment access and delivery

Linkage to HCV careAccess to HCV drugsPrimary care–based therapyMethadone-based directly observed therapyAccess to specialty careTelemedicineSlide65

Make a Change to Reduce HARM