The Pursuit of Hepatitis C Elimination

Learning Objectives • Demonstrate knowledge of HCV epidemiology and HCV elimination goals • Offer guideline-based HCV testing and identify people at risk for HCV infection • Provide patient-centered counseling regarding chronic HCV infection and the benefits of HCV cure

PREACTIVITY QUESTIONS

The Call for Pharmacists

A Central Role in HCV Elimination Office of HIV/AIDS and Infectious Disease Policy, US Department of Health and Human Services1

• Updated: 2014–2016 – Recognizes the need to expand the use of pharmacists and midlevel practitioners in the provision of viral hepatitis care and treatment – Identifies pharmacies as an important part of improving prevention, care, and treatment of viral hepatitis

HCV elimination begins with increased access to screening, diagnosis, and linkage to care.

HCV, hepatitis C virus.

1. DHHS. Action Plan for the Prevention, Care, & Treatment of Viral Hepatitis 2014−2016. 2014. https://www.hhs.gov/sites/default/files/viral-hepatitis-action-plan.pdf. Accessed June 1, 2019; 2. Pol S, Parlati L. Liver Int. 2018; 38(suppl 1):28-33.

HCV Is Common

Estimated Number of People Living With HCV 2013−2016

HCV-Infected Persons 0‒10,000 10,001‒25,000 25,001‒50,000 50,001‒75,000 75,001+

Emory University Coalition for Applied Modeling for Prevention (CAMP). https://hepvu.org/resources/#/. Accessed May 27, 2019.

HCV Incidence Is Increasing From 2010−2014, new HCV cases in the United States

INCREASED BY 250%

WITH AN ESTIMATED

30,500 NEW CASES IN 2014

= 0.7 cases/100,000 people 2010 Centers for Disease Control and Prevention (CDC). 2016. https//www.cdc.gov/hepatitis/statistics/2014surveillance/commentary.htm#hepatitis. Accessed May 27, 2019; Image adapted from: Emory University CAMP. www.hepvu.org. Accessed May 27, 2019.

2014

Distribution of Viremic Cases,

by Subpopulation Total Viremic Cases, %

100

Active Military

90

Nursing Home Residents

80

Homeless People

70

Incarcerated People

60

Household Members

50 40 30 20 10 0

Number of HCV Cases, Millions

The Hidden Burden of HCV in the United States 8 7

Conservative Estimate Upper Limit of Estimate

6 5 4 3 2 1 0 NHANES Estimate

HCV Cases Not Included in NHANES

Estimated Total HCV Cases

NASEM, National Academies of Sciences, Engineering, and Medicine; NHANES, National Health and Nutrition Examination Survey.

Razavi H. Modeling the elimination of hepatitis C in the United States. In: Strom BL, Buckley GJ, eds. NASEM. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report. Washington, DC: National Academies Press; 2017: Appendix B.

HCV Is the Most Common Blood-Borne Infection in the United States 3,500,000

Prevalence, N

3,000,000

~3,300,000

Unaware of Infection Aware of Infection

A low estimate that excludes individuals who are homeless, institutionalized, in prison, or in the military2,3

2,500,000 2,000,000 1,500,000 1,000,000

~1,100,000

~1,100,000

2,475,000

231,000 715,000

500,000

869,000

825,000 385,000

0 HIV/AIDS

HBV

HCV

HBV, hepatitis B virus.

1. Figure adapted from Colvin HM, Mitchell AE, eds. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academies Press; 2010. https://www.cdc.gov/hepatitis/pdfs/iom-hepatitisandlivercancerreport.pdf; 2. Denniston MM, et al. Ann Intern Med. 2014;160(3):293-300; 3. Chak E, et al. Liver Int. 2011;31(8):1090-1101.

HCV Is Deadly

The Natural History of the Disease Years 20−25 Years Normal Liver

HCV INFECTION

Chronic Hepatitis

Fibrosis  Cirrhosis

25−30 Years • HCC • ESLD • Death

55−85 will develop chronic HCV if untreated

20−30 will develop cirrhosis

1−5 will die from HCC or ESLD

OF EVERY 100 PERSONS INFECTED WITH HCV

ESLD, end-stage liver disease; HCC, hepatocellular carcinoma.

Lingala S, Ghany MG. Gastroenterol Clin North Am. 2015;44(4):717-734; 2. Image adapted from Hepatitis C Online. 2015. https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all. Accessed May 27, 2019.

HCV Kills 20,000 Americans Per Year

More Than HIV, TB, and 58 Other Infections Combined Annual Number of HCV-Related Deaths vs Other Notifiable Infectious Conditions in the US, 2003–2013 Number of Deaths

30,000 25,000

Other Notifiable Infectious Conditions

20,000 15,000

HCV

10,000 5,000 0 2003

2004

2005

2006

2007

2008

Year TB, tuberculosis.

CDC. 2016. https://www.cdc.gov/nchhstp/newsroom/2016/hcv-mortality.html. Accessed May 27, 2019.

2009

2010

2011

2012

2013

Baby Boomers

Disproportionately Affected by HCV

75

73

%

of individuals living with HCV

%

of deaths attributed to HCV

More than 15,000 deaths each year 1. CDC. Last updated November 2018. https://www.cdc.gov/hepatitis/populations/1945-1965.htm. Accessed May 27, 2019; 2. CDC. 2012. https://www.cdc.gov/nchhstp/newsroom/2012/hcvtesting-recs-pressrelease.html. Accessed May 27, 2019; 3. CDC. 2016. https://www.cdc.gov/media/releases/2016/p0504-hepc-mortality.html. Accessed May 27, 2019.

Placing Baby Boomers’ HCV Risks in Perspective • Time and place of birth • Any current or past injection drug use • Received blood transfusion before July 1992 • Received clotting factor concentrate before 1987 • HIV/AIDS

CDC. Last updated November 2018. https://www.cdc.gov/hepatitis/populations/1945-1965.htm. Accessed May 27, 2019.

But the Face of HCV Is Changing Acute HCV Incidence: US 2001–2016

2.5 2.0

By Sex 1.5

0–19 Years 20–29 Years 30–39 Years 40–49 Years 50–59 Years ≥60 Years

Reported Cases per 100,000 Population

Reported Cases per 100,000 Population

3.0

By Age Group

1.5 1.0 0.5 0.0 2001

2004

2007

2010

2013

2016

Male Female

1.0

0.5

0.0 2001

Year CDC. Last updated April 2018. https://www.cdc.gov/hepatitis/statistics/2016surveillance/index.htm. Accessed May 27, 2019.

2004

2007

2010

Year

2013

2016

An Increasingly Bimodal Age Distribution An Urban Crisis Mirrored in Nonurban Regions

1000

Number of Individuals

800

2007

Example: Philadelphia 2011

600 400 200 0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 1000 800

2013

1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93

2015

600 400 200 0 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89

Data courtesy of Kendra Viner, PhD. Philadelphia Department of Public Health.

Age

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96

Two Epidemics Intertwined

HCV Infection Is a Serious Health Consequence of Injection-Drug Use • HCV antibody prevalence among people who inject drugs (PWID) is estimated to be 70% to 77%1

45 1 in 3 people who inject drugs acquires HCV infection in their first year of injecting2

%

TO

85

%

45% to 85% of individuals chronically infected with HCV are unaware of their status1

1. CDC. Surveillance for Viral Hepatitis—United States, 2015. https://www.cdc.gov/hepatitis/statistics/2015surveillance/pdfs/2015HepSurveillanceRpt.pdf. Accessed May 27, 2019; 2. Hagan H, et al. Am J Epidemiol. 2008;168(10):1099-1109.

What Do We Mean by PWID? Lifetime PWID

MAT

Active PWID NSP

Lifetime PWID = Active Injecting + Past Injecting • Active PWID may participate in – Medication-assisted treatment (MAT) – Needle and syringe programs (NSPs)

• Past PWID may have acquired HCV infection with very limited injection experience

Image source: Larney S, et al. 4th International Symposium on Hepatitis Care in Substance Users. October 7−9, 2015; Sydney, Australia. Presentation.

Drug Addiction Is a Chronic, Relapsing Brain Disease – Compulsive drug seeking – Self-destructive behaviors – Continued use despite harmful consequences

• Brain changes are long-lasting • Disease-persistence rate is equivalent to that of other chronic diseases: T2DM, hypertension, asthma

Comparison of Disease-Persistence Rates Between Drug Addiction and Other Chronic Illnesses2 80

Patients With Disease Persistence,%

• Drugs change brain function and structure1

70 50 to 70

60 50

50 to 70

40 to 60 30 to 50

40 30 20 10 0 Drug Addiction

T2DM

Hypertension

Asthma

T2DM, type 2 diabetes mellitus.

1. NIH. National Institute on Drug Abuse. Last updated July 2018. https://www.drugabuse.gov/publications/media-guide/science-drug-abuse-addiction-basics. Accessed May 27, 2019; 2. NIH. National Institute on Drug Abuse. Last updated July 2018. https://www.drugabuse.gov/publications/drugs-brains-behavior-science-addiction/treatment-recovery. Accessed May 27, 2019.

Heroin Use Continues to Increase in Most Demographic Groups 2002−2004

2011−2013

Change, %

2.4 0.8

3.6 1.6

50% 100%

3

1.8 3.5 1.2

1.6 7.3 1.9

— 109% 58%

2

1.4 2.0

3.0 1.7

114% —

Heroin Addiction and Overdose Deaths

SEX

286% Increase in Heroin-Related Overdose Deaths (per 100,000 people)

AGE, YEARS

5.5 2.3 1.6

62% 77% 60%

1

6.7 4.7 1.3

60% — 63%

0

Heroin Addiction (per 1000 people) 2006

2005

2004

4.2 4.3 0.8

2003

None Medicaid Private or other

2002

HEALTH INSURANCE COVERAGE

National Survey on Drug Use and Health 2002-2013/National Vital Statistics System 2002-2013. Last updated July 2015. http://www.cdc.gov/vitalsigns/heroin. Accessed May 27, 2019.

2013

3.4 1.3 1.0

2012

Less than $20,000 $20,000−$49,999 $50,000 or more

2011

ANNUAL HOUSEHOLD INCOME

2010

Non-Hispanic White Other

2009

RACE/ETHNICITY

2008

12−17 18−25 26 or Older

2007

Male Female

Drug Overdose Deaths in the US CDC, 2017

• Overdose deaths in 2017: N=70,237 • 68% of all overdose cases were opioid-related

Statistically Significant Drug Overdose Death Rate Increase From 2016 to 2017

– Unintentional (84%) – Unintentional overdose death rate has increased 5-fold since 1999

• Highest drug overdose death rates per 100,000 population – – – – –

West Virginia: 57.8 Ohio: 46.3 Pennsylvania: 44.3 District of Columbia: 44.0 Kentucky: 37.2

Statistically Significant Increase

CDC. Last updated December 2018. https://www.cdc.gov/drugoverdose/data/statedeaths.html. Accessed May 27, 2019.

Yes

No

Overdose Deaths, by Type of Opioid Deaths per 100,000 Population

United States, 2000−2016

14 12 10

Any Drug Other Semisynthetic Opioids (eg, fentanyl, tramadol) Heroin Natural and Semisynthetic Opioids (eg, oxycodone, hydrocodone) Methadone

8 6 4 2 0 2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

Year CDC. Last updated December 2018. https://www.cdc.gov/drugoverdose/data/analysis.html. Accessed May 27, 2019.

2010

2011

2012

2013

2014

2015

2016

Preventing Opioid Overdose Is There a Role for the Pharmacist?

Opioid Overdose Prevention Toolkit

SAMHSA. Opioid Overdose Prevention Toolkit. HHS publication (SMA) 18 4742; 2018. https://store.samhsa.gov/product/Opioid-Overdose-Prevention-Toolkit/SMA18-4742.

Accessed April 11, 2019.

HIV/HCV Coinfection – HIV: sexual > blood-borne transmission – HCV: blood-borne > sexual transmission

• Coinfection is common1 – 10%–30% of persons with HIV have HCV coinfection – Injection drug use and sexual transmission in men who have sex with men (MSM) are predominant risk factors

• HIV independently associated with advanced liver disease in HIV/HCV coinfection2

Liver Fibrosis Versus Age Among Persons With HIV/HCV Coinfection and Persons With HCV Monoinfection2 14

Predicted FibroScan Score, kPa

• Shared routes of transmission1

HIV/HCV

13 12

HCV

11 10 9 8

9.2

7 6 30

35

40

45

50

55

Age, Years kPa, kilopascal: a unit of pressure.

1. CDC. Last updated February 2018. https://www.cdc.gov/hepatitis/hiv-hepatitis-coinfection.htm. Accessed May 27, 2019; 2. Kirk GD, et al. Ann Intern Med. 2013;158(9):658-666.

60

HCV Sexual Transmission in MSM Risk Factors: Case-Control Studya

• Sex practices – – – –

Receptive, unprotected anal intercourse Traumatic sex: fisting, use of sex toys Group sex; increased number of partners History of STI

Odds Ratio for HCV Transmission • 2 sexual risks: 9.2 (3.5−23.9) • ≥3 sexual risks: 23.5 (9.5−58.3)

• Drug practices – Association with noninjection recreational drug use • Methamphetamines, GHB, X, ketamine, alkyl nitrates (eg, amyl nitrate)

– No association with heroin, cocaine, or marijuana

GHB, gamma hydroxybutyrate; STI, sexually transmitted infection; X, 3,4-methylenedioxymethamphetamine (MDMA; also commonly known as ecstasy or molly). a60 HCV/HIV, 130 HIV-matched controls.

Danta M, et al. AIDS. 2007;21(8):983-991.

Putting HCV Test Results in Clinical Context Sequence for Identifying HCV Infection REFLEX HCV TESTING HCV Ab Plus HCV RNA if HCV Ab+ Ab Negative

Ab Reactive HCV RNA

No HCV Ab Detected

Not Detected

Detected

STOP

No Current HCV Infection

Current HCV Infection

Additional Testing as Appropriate

Link to Care

Caution: Consider recent exposure and Ab-negative window period CDC. MMWR Morb Mortal Wkly Rep. 2013;62(18):362-365.

Population and Individual Considerations Who Should Be Treated?

POPULATION LEVEL

INDIVIDUAL LEVEL

Risk of HCV transmission

Risk of liver-related morbidity and mortality

Highest Prevalence of PWID ≤25 Years of Age

• HIGHER RISK OF HCV TRANSMISSION • Lower risk of advanced liver disease

Grebely J, et al. Clin Infect Dis. 2013;57(7):1014-1020.

45 Years of Age • Moderate risk of HCV transmission • Moderate risk of advanced liver disease

≥65 Years of Age

• HIGHER RISK OF ADVANCED LIVER DISEASE • Lower risk of HCV transmission

HCV Guidance Recommendations for Testing, Management, and Treatment • Recommendations for When and in Whom to Initiate Treatment – Treatment is recommended for ALL patients with chronic HCV infection, except those with a short life expectancy that cannot be remediated by treating HCV, by transplantation, or by other directed therapy

• Goal of Treatment – Reduce all-cause mortality and liver-related adverse health consequences, including ESLD and HCC, by the achievement of virologic cure

AASLD/IDSA. When and in Whom to Initiate HCV Therapy. Last updated September 2017. https://www.hcvguidelines.org/evaluate/when-whom. Accessed May 27, 2019.

So, How Are We Doing?

HCV Care Cascade: US, 2016 HCV Testing and Linkage to Care 140,000

Baby Boomers

128,420

Number of People

120,000

Young Adults (Age 18-39 Years)

105,859

100,000 82,662 80,000

64,542

67,223

Efforts are needed to identify alternative HCV testing sites and linkage-to-care interventions for populations that have a high HCV burden and do not access health care through traditional means such as primary care clinics.

60,000 42,263

40,000 20,000 0

8.1%

3.9%

HCV Antibody Positive

82.4%

78.1%

Received RNA Test

63.5%

65.5%

HCV RNA Positive

Reau N, et al. AASLD ─ The Liver Meeting 2018. November 9–13, 2018; San Francisco. Abstract 1567.

15,724

9.2%

32.0%

23.4%

3906

5024

Saw HCV Treater

22.6%

884

Received Treatment

National Academies of Medicine A National Strategy, March 2017

• What are the strategic targets for eliminating HCV in the United States?

– – – –

90% reduction in HCV incidence relative to 2015 Depends on diagnosing 70,000–110,000 cases annually 28,000 HCV-related deaths averted by 2030 65% reduction in HCV-related mortality by 2030 2020

2025

2030

Achieving the National Academies Targets Number Needed to Be Diagnosed per Year

110,000

89,000

• This will require – Treatment without restrictions on severity of disease – Consistent ability to diagnose new cases, even as prevalence decreases NASEM. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report. Washington, DC: The National Academies Press; 2017.

70,000

HCV Testing in Baby Boomers and PWID USPSTF and AASLD/IDSA Recommendations Recommendations • One-time HCV testing is recommended for persons born between 1945 and 1965 (birth cohort; baby boomers) without prior ascertainment of risk1,2,a • All individuals outside of the birth cohort who have an HCV risk factor should be tested1 – Persons with continued risk of HCV exposure should be tested periodically2 – Evidence on how often testing should occur in these persons is lacking

• Annual HCV testing is recommended for PWID and for HIV-infected men who have unprotected sex with men2 • At least annual HCV-RNA retesting following successful HCV treatment or spontaneous viral clearance is recommended for sexually active MSM and PWID with recent or ongoing injection drug use2 − More frequent risk-based testing is recommended, if indicated − HCV Ab will remain positive in the majority of people and should not be used to test for reinfection Ab, antibody; USPSTF, US Preventive Services Task Force. aRegardless of country of birth (AASLD/IDSA).

1. Moyer VA, USPSTF. Ann Intern Med. 2013;159(5):349-357; 2. AASLD/IDSA. Testing, Evaluation, and Monitoring of Hepatitis C. Last updated September 2017. https://www.hcvguidelines.org/evaluate. Accessed May 27, 2019.

Who Else Should Be Tested for HCV? Other Risk Behaviors • Intranasal illicit drug use • Percutaneous exposures in an unregulated setting; eg, tattooing • Sharing of other blood-contaminated personal items; eg, razors

Risk Exposures • • • • • •

Ever incarcerated Children born to HCV-infected women Long-term hemodialysis Recipients of transfusions or organ transplants before July 1992 Received clotting factor concentrates before 1987 Healthcare workers after a needle-stick or mucosal exposure to HCV-infected blood

Other Indications • • • •

HIV infection Persons about to start HIV preexposure prophylaxis (PrEP) Solid-organ donors Unexplained chronic liver disease and/or chronic hepatitis

AASLD/IDSA. HCV Testing and Linkage to Care. 2018. https://www.hcvguidelines.org/evaluate/testing-and-linkage. Accessed May 27, 2019.

Linkage and Engagement in HCV Care The Patient’s Reality1,2

Limited access to health care Poor quality of life Alcohol consumption Use of multiple substances Homeless or living in temporary accommodations (shelter, prison) Poorly educated (secondary education or less)

“I am treated like a criminal and this makes it hard to take care of my health.”

“There are no friendly health care services near me where I live.”

“I would like to give up drugs, but I cannot get help.”

“I cannot get opioid-substitution therapy/syringes because it is illegal.”

“Health care workers do not trust me, as if I just want drugs.”

“Without clean needles and syringes, I have to share.”

Image source: Ramers CB. International Conference on Viral Hepatitis (ICVH 2016). March 14-15, 2016; San Francisco, CA. Adapted from: 1. Bamvita JM, et al. Hepat Res Treat. 2014; 2014:631481; 2. Harris M, et al. Hepatitis C testing & treatment for PWID: barriers and facilitators to hepatitis C treatment for people who inject drugs. World Health Organization (WHO). Published 2012. http://ljwg.org.uk/wp-content/uploads/2013/09/Barriers-and-facilitators-to-hepatitis-C-treatment-for-PWID-A-qualitative-study-June2012-rev-5.pdf. Accessed May 27, 2019.

Engagement in HIV/HCV Care

Increasing Proportion of Missed Intake Appointments and Failure to Establish HCV Care Proportion of and Risk Factors for Missed HCV Intake Appointments Year

Proportion of Missed Intake Appointments, % (n/N)

2014

17.2 (16/93)

2015

19.0 (18/95)

2016

25.6 (23/90)

Risk Factors for Missing HCV Intake Appointment: OR, CI, and P Value History of mental health disorder

OR 1.97; 95% CI 1.08–3.59; P=0.027

CD4 count <200 cells/L

OR 4.26; 95% CI 1.42–13.79; P=0.01

Active drug use

OR 1.92; 95% CI 1.03–3.58; P=0.039

Nonwhite

OR 2.13; 95% CI 1.17–3.88; P=0.013

CI, confidence interval; OR, odds ratio.

Cachay et al. Open Forum Infect Dis. 2018;5(7):ofy173.

Providersâ&#x20AC;&#x2122; Barriers to Referral and Treatment Outdated Clinical Data and/or Attitudes?

Nonreferral and Nontreatment in a Testing/Linkage Program (Denver) Reasons Not Referred to HCV Care

Number of HCV-Infected Individuals

60 40 20

46

55

29 11

14

14

Mental Illness

Referral Declined

Lost to Follow-up

0 Medical Diseases

Not Documented

Reasons Not Treated for HCV

30

23

Substance Abuse

28

20 10

4

4

Mental Illness

Substance Abuse

8

9

Medical Disease

Work Ongoing

0

Muething I, et al. ID Week 2015. October 7â&#x20AC;&#x201C;11, 2015; San Diego, CA. Poster 1029.

Lost to Follow-up Not Advanced Liver Disease

Real-World Evidence

Feasibility and Efficacy of Treating HCV in PWID • REALITIES – Baseline drug use – Continued injection drug use during DAA therapy – Concurrent MAT for opioid dependence – HIV/HCV coinfection

93%−95% SVR12 among PWID with recent or ongoing injection drug use1,2 Near-identical SVR12 rates achieved in MAT vs non-MAT PWID3-10 No drug-drug interactions with MAT9,10 No negative impact of HIV/HCV coinfection on SVR11-16

DAA, direct-active antiviral; SVR, sustained virologic response; SVR12, SVR at 12 weeks.

1. Rockstroh JK. European Association for the Study of the Liver. The International Liver Congress™ − EASL 2017. April 19−23, 2017; Amsterdam, The Netherlands; 2. Alimohammadi A, et al.

Open Forum Infect Dis. 2018;5(6):ofy120; 3. Grebely J, et al. Clin Infect Dis. 2016;63(11):1405-1411; 4. Zeuzem S, et al. Ann Intern Med. 2015;163(1):1-13; 5. Dore GJ, et al. Ann Intern Med. 2016;165(9):625-634; 6. Grebely J, et al. Clin Infect Dis. 2016;63(11):1479-1481; 7. Grebely J, et al. J Hepatol. 2017;66(suppl 1):S513-S514; 8. Puoti M, et al. J Hepatol. 2018;69(2):293-300; 9. Kiser JJ. Top Antivir Med. 2016;24(3):106-110; 10. Drugs@FDA. 2018. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed May 27, 2019; 11. Osinusi A, et al. JAMA. 2015;313(12): 1232-1239; 12. Naggie S, et al. N Engl J Med. 2015;373(8):705-713; 13. Rockstroh JK, et al. Lancet HIV. 2015;2(8):e319-e327; 14. Sulkowski MS, et al. JAMA. 2015;313(12):1223-1231; 15. Wyles D, et al. Clin Infect Dis. 2017;65(1):6-12; 16. Rockstroh JK. Clin Infect Dis. 2018;67(7):1010-1017.

What Does Your Patient Need to Know About HCV? • HCV is a serious and potential deadly disease that is associated with high risk of cirrhosis and liver cancer • The virus can be transmitted to others through – Shared use of drug paraphernalia or other blood-contaminated objects (eg, razors) – Sexual activity, especially among MSM – Pregnancy; maternal-child transmission

• Cost should not be a barrier to initiation of HCV treatment!

• HCV treatment is highly effective, including in PWID on MAT or continuing injection drug use; and in HIV/HCV coinfection – – – – –

Treatment will be managed by an HCV-care provider Treatment may be as simple as 1−3 pills per day, and as brief as 8−12 weeks in duration The medications are well tolerated The full treatment course must be completed Post-treatment follow-up is essential

• HCV reinfection is possible — risk reduction following treatment is critical!

AASLD. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. Last updated September 2017. http://www.hcvguidelines.org/evaluate/when-whom. Accessed May 27, 2019.

Benefits of Achieving HCV Cure The Individual and the Community1-3

Decreased Transmission

CURE Improved Clinical Outcomes

Hepatic

Extrahepatic

 Cirrhosis  Decompensation  HCC  Transplantation

Improved quality of life  All-cause mortality  Malignancy  Diabetes  Cardiovascular disease  Renal manifestations  Neurocognitive manifestations

HCC, hepatocellular carcinoma.

1. Image adapted from: Smith-Palmer J, et al. BMC Infect Dis. 2015;15:19; 2. Negro F, et al. Gastroenterology. 2015;149(6):1345-1360; 3. George SL, et al. Hepatology. 2009;49(3):729-738.

Copay Assistance Programs Cost Should Not Be a Barrier

www.healthwellfoundation.org

www.copays.org

www.mygooddays.org

www.tafcares.org

www.panfoundation.org

See also manufacturersâ&#x20AC;&#x2122; coupons for financial assistance (applies only to commercial insurance plans).

Harm Reduction

Reducing the Negative Consequences of IDU1 • MAT – Methadone, buprenorphine, other opiate substitutes – Reduction in the number and severity of relapses due to opiate use

• NSPs – Reduction in incidence of HCV infection and reinfection

• Naloxone access – A parenterally administered medication that rapidly reverses the effects of opioids – Training for persons at risk and individuals likely to witness an OD2

• Mental-health services colocated with MAT/NSP3 • Education, counseling, and outreach

IDU, injection drug use; OD, overdose.

1. Harm Reduction Coalition. http://harmreduction.org/. Accessed May 27, 2019; 2. Community Management of Opioid Overdose. Geneva, Switzerland: WHO; 2014. https://www.ncbi.nlm.nih.gov/books/NBK264297/. Accessed May 27, 2019; 3. Islam N, et al. Lancet Gastroenterol Hepatol. 2017;2(3):200-210.

A Functional Definition of Harm Reduction Harm reduction is any positive change, as defined by the person at risk for harm. It is meeting people where they are and providing the tools and information they need to keep themselves and those around them healthy.

Dan Biggs, Chicago Recovery Alliance

Where Does Harm Reduction Fall Within the HCV Treatment Cascade?

Identified Chronic HCV-Infected Population, %1

100

HARM REDUCTION2

80 60 40

9%

20 0

100% Chronic HCVInfected

50%

43%

Diagnosed and Access to Aware Outpatient Care

27% HCV RNA Confirmed

17%

16%

Underwent Liver Prescribed HCV Biopsy Treatment

1. Yehia B. PLoS One. 2014;9(7):e101554; 2. Harm Reduction Coalition. https://harmreduction.org/. Accessed May 27, 2019.

Achieved SVR

Harm Reduction Does Not End With Cure Reinfection in PWID: Realities and Strategies

• There will be cases of HCV reinfection1 – Risk increases with higher injection frequency – But there is no overall difference in reinfection rate, even among individuals currently injecting or on MAT

• But we must concomitantly scale up harm-reduction measures

HCV Treatment as Prevention: Treat More  Eliminate Sooner2 Reinfection, %

250 200 150

Treat 1% Treat 2% Treat 4% Treat 8% Treat 10%

– MAT – NSPs – Increased intensity of HCV management, eg, directly observed treatment – Patient education and counseling AND – Increased HCV treater workforce

100 50 0 2014

2016 2018 2020

2022 2024

2026

2028

2030

1. Grebely J, Dore GJ. Clin Liv Dis (Hoboken). 2017;9(4):77-80; 2. Grebely J, et al. Nat Rev Gastroenterol Hepatol. 2017;14(11):641-651.

HCV Treatment as Prevention Swiss HIV Cohort

All HCV Infections

• Phase A

• Phase B – – – –

EBR/GZR or other DAAs Phase duration: 9 months 157 treated SVR: 99.5%

• Phase C – Rescreening – Phase duration: 9 months

Incident Infections Total Infections, Number

– HCV RNA screening Q6mo – Phase duration: 9 months – 3722 screened; 4.8% RNA+

EBR, elbasvir; GZR, grazoprevir; Q6mo, every 6 months.

Braun DL, et al. CROI 2018. March 4−7, 2018; Boston, MA. Abstract 81LB.

160

Chronic Infection 147

140

49%

120 100

92.5%

Decrease

80

Decrease

60 40

31 16

20

12

0 Phase A Oct 2015– Jun 2016

Phase C Mar 2017– Nov 2017

Phase A Oct 2015– Jun 2016

Phase C Mar 2017– Nov 2017

Critical Roles for the Pharmacist in HCV Elimination1,2 • Increase screening and diagnosis capacities • Extend services to difficult-to-reach populations • Improve linkage to care and engagement in treatment • Improve HCV medication selection and access • Collaborate on multidisciplinary teams to optimize HCV treatment • Monitor HCV treatment and medication adherence • Provide disease state and behavioral-risk education • Support harm-reduction measures 1. Gauthier TP, et al. J Am Pharm Assoc (2003). 2016;56(6):670-676; 2. Cook C, Buchanan R. Pharm J. 2017; 299(7907).

SELECTED MODELS AND STUDIES Pharmacy-Based HCV-Related Services

Model: Large Retail Pharmacy Point-of-Care HCV Testing1,2

• Background: POC testing can increase the number of individuals diagnosed; however, linkage to care which remains a major challenge, is essential for improving patient outcomes • Design – Participating markets were selected within lower-income areas of major metropolitan cities – Each market had 5 pharmacy sites; testing was performed at each site once weekly – 1 phlebotomist was assigned per market; each was individually trained on administration of HCV-Ab testing and interpretation of results – Individuals were recruited by direct advertising at each store

• Primary objective: To identify HCV prevalence using birth cohort and high-risk factor screening at large retail pharmacies and link HCV-Ab+ individuals with a pathway to care POC, point of care.

Kugelmas M, et al. Gastroenterol Hepatol (N Y). 2017;13(2):98-104.

Participating Markets

New York, NY Philadelphia, PA Chicago, IL Miami, FL Houston, TX

Dallas, TX San Antonio, TX Phoenix, AZ Oakland, CA

Large Retail Pharmacy: POC Testing Results and Conclusions

Testing and Pathway to HCV Care Total screened n=1298

HCV antibody positive n=103 (8%)

• Study conclusions

HCV antibody negative n=1193 (92%)

Unable to reach patient n=12 (12%)

Contacted with results n=91 (88%)

Unable to reach patient n=35 (38%)

21−28-day follow-up n=56 (62%)

Confirmed HCV RNA test n=29 (52%)

HCV management specialist unable to confirm HCV RNA test was done n=27 (48%)

Kugelmas M, et al. Gastroenterol Hepatol (N Y). 2017;13(2):98-104.

– Retail pharmacy–based HCV screening in high-risk individuals using POC technology is effective – Other barriers to HCV care linkage need further exploration and creative solutions

Model: HCV Testing in NSP Pharmacies Pilot Study: The London Joint Working Group

• Number of persons screened: 216 • Number meeting inclusion criteria: 178 • Aims – Develop effective POC patient-centered HCV testing and support pathways to treatment for PWID – Determine HCV prevalence within this population – Provide information/education regarding HCV, antiviral therapy, and safe injecting practices

Individuals Screened, n (%)

HCV Antibody Positive, n (%)

Male

141 (80.1)

75 (53.2)

Female

35 (19.9)

19 (54.3)

18−29

9 (5.2)

<5

30−39

52 (30.2)

32 (61.5)

40−49

52 (30.2)

25 (48.1)

50−59

46 (26.9)

32 (69.6)

>60

13 (7.6)

<5

Yes

123 (69.9)

72 (58.6)

No

42 (23.9)

19 (45.2)

11 (6.3)

4 (36.4)

Sex

Age (6 missing)

Previously Tested

Unknown

October 2017 to March 2018.

HCV Testing in NSP (Needle and Syringe Provision) Community Pharmacies Pilot (Phase 1). London Joint Working Group. May 2018. Presentation.

The London Joint Working Group Pilot Study Conclusions

• The pilot demonstrated that providing HCV tests within NSP community pharmacies can be an effective tool for identifying HCV+ PWID and referring them for further testing and treatment • Treating with HCV antiviral therapy directly in NSP pharmacies has the potential for higher uptake of treatment by service users testing positive for HCV • Educating service users regarding HCV treatments and safer injection practices should be integral to any pharmacy testing program • Practical recommendations – Pharmacy training is essential prior to HCV testing going live – Pharmacy training should include practical demonstrations: both testing and counseling – All pharmacy counter staff should be trained HCV Testing in NSP (Needle and Syringe Provision) Community Pharmacies Pilot (Phase 1). London Joint Working Group. May 2018. Presentation.

Model: Community Pharmacyâ&#x2C6;&#x2019;Based HCV Education

Increasing Awareness, Screening, and Linkage to Care Knowledge and Awareness Questionnaire Responses Before and After HCV Education, N=16a Strongly Disagree

Disagree

Neutral

Strongly Agree

Agree

Before

After

Before

After

Before

After

Before

After

Before

After

I know what HCV is, n

2

0

2

0

3

0

6

2

3

14

I know how HCV is spread, n

3

0

6

0

2

0

4

2

1

14

I know how HCV is treated, n

5

0

6

0

3

0

2

3

0

13

I know who should get treated for HCV, n

3

0

4

0

4

0

3

4

2

12

I know when HCV is treated, n

4

0

7

0

3

2

2

3

0

11

N, number of responses aP<0.001 for difference in pre- and post-HCV education responses for each question.

Isho NY, et al. J Am Pharm Assoc (2003). 2017;57(suppl 3):S259-S264.

Study: The Rural Outpatient Setting

The Pharmacist’s Roles in HCV Care Under Collaborative Drug Therapy Management (CDTM) • A federal study of Indian Health Service (IHS) facilities to identify and address gaps in HCV treatment • Clinical pharmacists’ roles under the CDTM – Provide comprehensive HCV care under the supervision of a physician – Screen for and address lifestyle factors and comorbidities that may adversely affect HCV treatment outcomes – Act as case manager for patients diagnosed with HCV; link to other services – Provide other pharmacist services; eg, medication counseling, DDI identification, treatment monitoring Geiger R, et al. J Prim Care Community Health. 2018;9:1-5.

IHS Facilities Study

Screening to Diagnosis: Study Results and Conclusions • Key findings: screening to confirmatory testing

HCV Ab+ (N=1789)

– 1789 patients identified as HCV Ab+ – 77% (1381) had a confirmation test performed – 67% (929) were positive for HCV RNA

• These data indicate that rural clinics can be successful in providing HCV diagnosis • Pharmacists can play a key role in rural HCV clinical services Geiger R, et al. J Prim Care Community Health. 2018;9:1-5.

RNA Test Documented YES 77%

RNA+ (n=929)

NO 33%

RNA‒ No Further Followup Needed (n=452)

Need RNA Confirmation (n=408)

Study: An HIV/HCV Primary Care Model

The Pharmacist’s Role in the Multidisciplinary Team • One of the first studies to identify the important role of pharmacists in increasing access to HCV treatment in difficult to treat populations • A higher proportion of patients received treatment in the primary care vs the specialty model – Similar rates of psychiatric disease – Higher frequency of substance use disorder in primary care model

• Cure rates in the primary care model were similar to those in the specialty model

Cachay E, et al. AIDS Research and Therapy. 2013;10(9):1-12.

Concluding Comments

Critical Opportunities for Pharmacists • Pharmacists are ideally placed in diverse practice settings to actively participate in HCV elimination • Community pharmacists can form effective relationships with patients in difficult-to-reach subpopulations and implement HCV testing, identification of at-risk individuals, education, and linkageto-care strategies • Pharmacists can extend HCV treatment capacity and impact through collaborative multidisciplinary care models and provide pharmacist-based services that enhance care

A CURE FOR ALL!