Contemporary Management of HIV-HCV Coinfection

Elizabeth Sherman, PharmD, AAHIVP

Faculty, South Florida - Southeast AIDS Education & Training CenterHIV/AIDS Clinical Pharmacist, Memorial Healthcare SystemAssistant Professor, Nova Southeastern Universityesherman@nova.edu

Disclosures

• The activity planners and speakers do not have any financial relationships with commercial entities to disclose.

• The speakers will not discuss any off-label use or investigational product during the program.

• This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation

Learning Objectives

• Apply current guidelines on hepatitis C virus (HCV) screening

• Manage patients with HCV infection while recognizing adverse effects and drug interactions

• Counsel patients regarding current HCV treatment options, timing of treatment, and key characteristics of current regimens

Introduction

Chronic Hepatitis C Virus (HCV) Is a Progressive Disease

Chronic HCV frequently has few or no symptoms and can progress without signs for decades[1]

Most patients with chronic HCV are asymptomatic until serious liver complications arise[2]

HEALTHY LIVER FIBROTIC LIVER CIRRHOTIC LIVER

1. CDC. MMWR Morb Mortal Wkly Rep. 1998;47(RR-19):1-39. 2. Heidelbaugh JJ, et al. Am Fam Physician. 2006;74:756-762.

Slide credit: clinicaloptions.com

HCV in the US: Gaps in Current Practice

Pts

(%)

n = 3,500,000 1,743,000 1,514,667 952,726 581,632 555,883 326,859

0

20

40

60

80

100

ChronicHCV Infected

Diagnosedand

Aware

Access to Outpatient

Care

HCV RNAConfirmed

UnderwentLiver

Biopsy

Prescribed HCV

Treatment

AchievedSustained Viral

Response

50%43%

27%

17% 16%9%

Yehia BR, et al. PLoS One. 2014;9:e101554.

100%

Slide credit: clinicaloptions.com

Current All-Oral Therapies Highly Effective, Simple, Well Tolerated

IFN6 Mos

PegIFN/RBV 12 Mos

IFN12 Mos

IFN/RBV12 Mos

PegIFN12 Mos

2001

1998

2011

StandardInterferon

(IFN)

Ribavirin(RBV)

Peginterferon(pegIFN)

1991

PegIFN/RBV +DAA

IFN/RBV6 Mos

616

3442 39

55

70+

0

20

40

60

80

100

DAA + RBV ±PegIFN

90+2013

All–OralDAA±

RBV

Current95+

All-Oral Therapy

Direct-ActingAntivirals(DAAs)

Slide credit: clinicaloptions.com

Case 1:When and How to

Screen for Hepatitis

Case 1: 56-Yr-Old Woman Presenting to Primary Care

A 56-yr-old woman visits your office She has recently moved to the area

following a promotion and is looking for a primary care clinician She is not aware of having been tested for

HCV infection previously

Slide credit: clinicaloptions.com

1. Smith BD, et al. MMWR Recomm Rep. 2012;61(RR-4):1-32. 2. US Preventive Services Task Force. HCV Screening Guidelines 2013. 3. AASLD-IDSA. HCV Guidelines 2017.

Population Recommendation

Age One-time screening is recommended for persons born between 1945 and 1965, without ascertainment of HCV risk[1-3]

Risk One-time screening is recommended for persons with these risk factors[1,3]:History of illicit injection drug use (IDU) or intranasal illicit drug useHistory of long-term hemodialysisReceiving a tattoo in an unregulated facility/settingHealthcare workers upon accidental exposureChildren born to anti-HCV–positive mothersHistory of transfusion with blood or organ transplantationWere ever in prisonHIV infectionChronic liver disease/hepatitis with unknown cause, including elevated liver enzymes

Annual screening is recommended for current IDUs and HIV-infected MSM[3]

CDC, USPSTF, and AASLD/IDSA HCV Screening Recommendations

Hepatitis C Prevalence is Increased in Baby Boomers

Prevalence of Hepatitis C Antibody Positivity in US Population by Sex by Yr of Birth (NHANES III)

Screening recommended

Pre

vale

nce

of H

epat

itis

CP

ositi

ve (%

)

0

2

4

6

8

10

1910-19 1920-29 1930-39 1940-49 1950-59 1960-69 1970-79 1980-89 1990-99Yr of Birth

MaleFemale

Iwasaki K, et al. ISPOR 2010. Abstract PG17. Slide credit: clinicaloptions.com

Talking to Patients About Hepatitis C Testing

• Provide rationale for testing

• Provide reassurance about testing

• Obtain consent

Slide credit: clinicaloptions.com

Talking to Patients About Hepatitis C Testing

• Provide rationale for testing– It’s common

• Provide reassurance about testing– It’s curable

• Obtain consent– If it’s alright with you, I would like to test

you for hepatitis C today Slide credit: clinicaloptions.com

Back to Our Case

A 56-yr-old woman visits your office She has recently moved to the area

following a promotion and is looking for a primary care clinician

Routine hepatitis C antibody test: reactive

Slide credit: clinicaloptions.com

Recommended Testing Sequence for Identifying Current HCV Infection

HCV antibody testProvide care or link to care

Reactive

Nonreactive

Stop

HCV RNA test Detected

Not detected

No current HCV infection

Current HCV infection

Additional testing as appropriate

CDC. MMWR Morb Mortal Wkly Rep. 2013;62:362-365.

Slide credit: clinicaloptions.com

Recommendations for Additional Follow-up of Initial HCV Testing

• Quantitative hepatitis C RNA testing prior to initiation of antiviral therapy to document baseline viral load

• Testing for hepatitis C genotype—all genotypes can be treated, but genotype will guide choice of antiviral therapy

AASLD-IDSA. HCV Guidelines 2017.Slide credit: clinicaloptions.com

Counseling for HCV-Infected Individuals

Prevent HCV Transmission

• Avoid sharing toothbrushes, dental, shaving equipment

• Prevent blood contact; do not donate blood

• Avoid illicit drugs; avoid reusing or sharing drug paraphernalia

• Risk of sexual transmission is low, except for people with HIV, multiple partners, or STIs

Reduce Progression of Liver Disease

• Test for conditions that accelerate fibrosis (Hepatitis B and HIV)

• Evaluate for advanced fibrosis• Update vaccinations• Avoid alcohol

Slide credit: clinicaloptions.com

Recommendations for When and in Whom to Initiate HCV Treatment Treatment is recommended for all pts with

chronic hepatitis C infection, regardless of genotype– Except where life expectancy likely to be

short despite treatment or transplantation

AASLD-IDSA. HCV Guidelines 2017.Slide credit: clinicaloptions.com

HCV Virologic Cure Associated with Improved Outcomes

HR: 0.26 (95% CI: 0.14-0.49; P < .001)

30

20

10

0All-

Cau

se M

orta

lity

(%)

0 1 2 3 4 5 6 7 8 9 10Yr

P < .001

Without SVR

With SVR

30

20

10

0Live

r-R

elat

ed M

orta

lity

or

Live

r Tra

nspl

anta

tion

(%)

0 1 2 3 4 5 6 7 8 9 10Yr

P < .001

Without SVR

With SVR

Liver-Related Mortality or Liver TransplantationAll-Cause Mortality

Virologic cure does not protect against reinfectionvan der Meer AJ, et al. JAMA. 2012;308:2584-2593.

Slide credit: clinicaloptions.com

Fibrosis Staging

• Determines treatment (e.g., use of ribavirin) and treatment duration– Metavir Stage 0-2: No fibrosis or portal fibrosis– Metavir Stage 3-4: Advanced fibrosis or

cirrhosis• Noninvasive strategies: APRI (AST platelet

ratio index), FIB-4, FibroSure, FibroScanSlide credit: clinicaloptions.com

Case 2

Ongoing Management of HCV

Case 2: 45-Yr-Old Man With Hepatitis C Infection

A 45-yr-old man visits your office Diagnosed with chronic HCV in 2011,

previously treated with peginterferon and ribavirin– Noninvasive markers suggest Metavir

stage 2 (some fibrosis) Now expresses interest in hepatitis C therapy

after hearing positive reports about new oral treatments Slide credit: clinicaloptions.com

Case 2: Initial WorkupParameter FindingCoinfections HAV negative,

HBV negative, HIV negative

HCV genotype 1aHCV RNA 3,500,000 IU/mLFibroSure F2

Parameter FindingWBC 3500 cells/mm3

Hemoglobin 14 g/dLPlatelets 155/μLINR 1.0Albumin 3.8 mg/dLTotal bilirubin 1.2 mg/dLAST 68 IU/mLALT 64 IU/mLAlk phos 155 IU/mL

Creatinine 1.2 mg/dL

Many Options in 2017: Current All-Oral Regimens for Hepatitis C Infection

Regimen Approved Genotypes

Grazoprevir/elbasvir 1, 4Ombitasvir/paritaprevir/ritonavir 4

Ombitasvir/paritaprevir/ritonavir + dasabuvir 1

Sofosbuvir + daclatasvir 1, 3Sofosbuvir/ledipasvir 1, 4, 5, 6Simeprevir + sofosbuvir 1, 4Sofosbuvir/velpatasvir 1, 2, 3, 4, 5, 6Sofosbuvir/velpatasvir/voxilaprevir 1, 2, 3, 4, 5, 6

Effective options for every genotype

Single-pill formulations or2-pill combinations

Effective for all genotypes

HCV Drug Targets: Helpful Hints

• “-previr” – NS3 protease inhibitors

• “-buvir” – NS5B inhibitors

• “-asvir” – NS5A inhibitors

HCV Treatment: Get to Know Your Patient

HCVgenotype?

Presence of cirrhosis?

Previous HCV

therapy?

Helps tailor: Treatment

options

Treatment duration

Need for ribavirin

Key Resource: www.hcvguidelines.orgSlide credit: clinicaloptions.com

Adverse Events and Drug-Drug Interactions

Adverse Events

Newer hepatitis C medications do not have same adverse events as interferon and are generally well tolerated

Discuss most common adverse events and management strategies in pre-education session– Headaches: nonpharmacologic management

strategies, limits of OTC pain relievers and liver disease

– Anemia: still a concern when ribavirin needed Encourage patients to report bothersome or unusual

adverse events Slide credit: clinicaloptions.com

Ribavrin Considerations

• Most patients won’t need it!• If they do…

– Discuss contraception– Check baseline hemoglobin and test for

anemia through treatment– Counsel on anemia symptoms– Know that anemia can be managed for most

while completing HCV therapy Slide credit: clinicaloptions.com

Pretreatment: Look for Potential Drug–Drug Interactions

Review all herbals/supplements, prescription and OTC meds, including contraceptives and proton pump inhibitors

Ask about PRN usage of other drugs Consult with clinical pharmacist when

possible

Key Resource: www.hep-druginteractions.orgSlide credit: clinicaloptions.com

Drug Interactions in the HIV-HCV Coinfected Patient

• Priority population for treatment• SVR rates similar to HCV monoinfected[1,2]

• In HCV/HIV coinfection, treat HCV as though HCV monoinfected, but consider drug–drug interactions[3]

– Drug–drug interactions may require careful selection of HCV regimen or changes in HIV ART regimens

• Non-HIV providers require collaboration with the patient’s HIV provider

1. Naggie S, et al. N Engl J Med. 2015;373:705-713. 2. Wyles DL, et al. N Engl J Med. 2015;373:714-725. 3. AASLD/IDSA Guidelines. February 2016.

Slide credit: clinicaloptions.com

SIM +

SOFLDV/ SOF

SOF+

DCVPTV/RTV/

OBV + DSVPTV/RTV/

OBVEBV/ GZR

SOF/ VEL

SOF/VEL/ VOX

Atazanavir + RTV or COBI Χ √ ≈ ≈ Χ Χ √ Χ

Darunavir + RTV or COBI Χ √ √ Χ ≈ Χ √ √

Raltegravir √ √ √ √ √ √ √ √

Dolutegravir √ √ √ √ √ √ √ √

Elvitegravir/ COBI/FTC/ TDF

Χ Χ ≈ Χ Χ Χ ≈ ≈

Elvitegravir/ COBI/ FTC/ TAF

Χ √ ≈ Χ* Χ Χ √ √

Efavirenz Χ ≈ ≈ Χ Χ Χ Χ Χ

Rilpivirine √ √ √ Χ Χ √ √ √

Abacavir/lamivudine √ √ √ √ √ √ √ √

Emtricitabine/ TDF √

≈nephro-toxicity

√ √ √ √≈

nephro-toxicity

≈nephro-toxicity

Emtricitabine/ TAF √ √ √ √ √ √ √ √

√ No clinically significant interaction expected

≈ Potential interaction may require adjustment to dosage, timing of administration, or monitoring Χ Do not coadminister

HCV Interactions With ART

Other Selected Potential Drug–Drug Interactions with HCV Agents

AASLD/IDSA Guidelines. 2017.

Concomitant Medication SIM/SOF

LDV/ SOF

SOF/DCV

PTV/RTV/ OBV + DSV

PTV/RTV/OBV

EBV/ GZR

SOF/ VEL

SOF/VEL/VOX

Acid-reducing agents* X X X X X

Amiodarone X X X X X X X

Anticonvulsants X X X X X X X X

Digoxin X X X X X X

Ethinyl estradiol–containing products

X X

Glucocorticoids† X X X X X

PDE5 inhibitors X X X X

Rifamycin antimicrobials X X X X X X X X

St John’s wort X X X X X X X X

Statins X X X X X X X X

*eg, proton pump inhibitors such as omeprazole. †Including inhaled, intranasal.

Supporting Patients During Antiviral Therapy

AASLD-IDSA. HCV Guidelines 2017.

Key Resource: www.hcvguidelines.org

RecommendationsOffer clinic visits or telephone contact to ensure adherence and to monitor for adverse events and drug interactionsCBC, creatinine level, eGFR, hepatic function panel at week 4 and as clinically indicatedQuantitative HCV RNA at week 4 of treatment and again at 12wks after completion of treatment (SVR)

Slide credit: clinicaloptions.com

Post-Treatment Follow-up

Recommended Follow-up After Hepatitis C Treatment

Characteristic Follow-up

No advanced fibrosis (Metavir stage F0-F2) No hepatitis C follow-up

Advanced fibrosis (Metavir stage F3 or F4) Twice-yearly ultrasound surveillance for hepatocellular carcinoma

– If compensated cirrhosis (F4) also test for varices using baseline endoscopy

Ongoing hepatitis C risk or unexplained hepatic dysfunction

Test for recurrence or reinfection with quantitative hepatitis C RNA assay

Persistently abnormal liver tests Test for other causes of liver disease

No virologic cure Test for disease progression every 6-12 months with hepatic function panel, CBC, and INR

Consider retreatment options

Slide credit: clinicaloptions.com

Summary Patients born 1945-1965 should be screened for HCV infection

– Know risk-based screening recommendations Virtually all with HCV infection should be treated, regardless of

genotype and fibrosis– Prevents morbidity, progression of fibrosis, hepatocellular

carcinoma Current treatments include pangenotypic and ribavirin-free

options– > 95% rate of cure for most genotypes– Most therapies are 12 wks, ribavirin free, all oral, once daily

• Many patients can be treated in primary care setting– Counsel and monitor for adverse effects and drug interactions

This Presentation and resources are made possible by AETC grant award U1OHA29295 from the HIV/AIDS Bureau of the Health Resources Services Administration (HRSA), U. S. Department of Health and Human Services (HHS).

The information presented is the consensus of HIV/AIDS specialists within the SEAETC and does not necessarily represent the official views of HRSA/HAB

The AIDS Education and Training Center (AETC) Program is the training arm of the Ryan White HIV/AIDS Program. The AETC Program is a national network of leading HIV experts who provide locally based, tailored education, clinical consultation and technical assistance to healthcare professionals and healthcare organizations to integrate high quality, comprehensive care for those living with or affected by HIV.