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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Hepatitis C: Pre-treatment Evaluation
Jody Gilmore, ANP-BC, MSNViral Hepatitis Coordinator
Division of Infectious DiseasesPenn Presbyterian Medical Center
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Learning Objectives
Upon completion of this presentation, learners should be better able to:– Identify HCV pre-treatment needs for patients with HIV/HCV
co-infection– Explain importance of staging liver fibrosis– Review current HCV treatment options – Identify drug-drug interactions in the treatment of HIV/HCV patients
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
FacultyandPlanningCommitteeDisclosuresPleaseconsultyourprogrambookortheConferenceApp.
Off-LabelDisclosureThere will be no off-label/investigational uses discussed in this presentation.
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Treatment of HIV/HCV Coinfection: Factors to Consider
• HCV workup if starting DAA:– HCV genotype– HCV RNA – Staging of liver disease– Previous DAAs– HBV status
• HIV work-up if starting/switching ART:– HIV-1 RNA level– HLA B-5701 status– CD4+ cell count– Resistance testing
• All patients– Creatinine Clearance– Non-ART, non-DAA comedications– Comorbidities
AASLD/IDSAHCVGuidelines.2018.
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Past History: – Type 1 diabetes mellitus, insulin-dependent since age 7– HIV dx: 2012 (CD4=525 cells/mm3; HIV= 46 copies/mL)– Depression– Hepatitis C –recent screening due to elevated transaminases
• Medications:– Insulin– Elvitegravir/cobicistat//emtricitabine/tenofovir(TDF)– Sertraline
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Social History:– Works full-time, excellent private insurance– Past use IV methamphetamines- last used 2016– Denies alcohol intake, occasional marijuana– Husband also HIV+, suppressed viral load, plans to get tested
for hepatitis C
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
WHENTODOHCVSCREENING?ENTRYINTOHIVCAREAND….
RecommendationforHCVTestingforPersonsWithOngoingRiskFactors
RECOMMENDED RATING
AnnualHCVtestingisrecommendedforpersonswhoinjectdrugsandforHIV-infectedmenwhohaveunprotectedsexwithmen.
PeriodictestingshouldbeofferedtootherpersonswithongoingriskfactorsforHCVexposure.
IIa,C
Available at: www.hcvguidelines.org. Accessed April 28, 2016.
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Source: CDC, National Notifiable Diseases Surveillance System (NNDSS)
0
0.5
1
1.5
2
2.5
3
Repo
rted
cases/100
,000
pop
ulation
0-19yrs20-29yrs30-39yrs40-49yrs50-59yrs>60yrs
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Physical exam:– African American– Ht 5’ 11”, Weight 165 lbs– No hepatomegaly, stigmata of liver disease
• Laboratory data:– ALT 196; AST 205– Total bilirubin 0.8; Alb 4.0; INR 1.0– HCV RNA quant 5,134,675 copies/mL
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Laboratory data (cont)– WBC 4.5; Hgb 12.9 – Platelets 325– Creat 0.86– Hemoglobin A1c- 11.3 – HBsAg (-)– anti-HBc (-)– anti-HBs (+)– HAV IgG (+)– HLA B5701 negative
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Question:What would you do next?
A. Obtain AFP
B. Stage his liver fibrosis
C. Initiate sofosbuvir/ledipasvir, Genotype 1a
D. Post-pone treatment until Hgb A1c in normal range
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
How to Determine Liver Fibrosis Stage
Liver Biopsy Serum Markers TransientElastographyHCV FibroSure
age (years) x AST (U/L)platelets (109/L) x ÖALT (U/L)
AST (U/L) / AST (upper limit normal)platelets (109/L)
FIB-4 =
APRI =
Liver stiffness (kPa)
Liver fibrosisSterling RK. Hepatology 2006;43:1317-25.Kirk GD et al. Clin Infect Dis 2009;48:963-72.Chou R. Ann Intern Med 2013;158:807-20.
X 100
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Liver Stiffness Measurement (LSM) Ranges in Chronic Liver Disease
METAVIRScore
F0– F1 F2 F3 F4
Liver Fibrosis
Mild Moderate Severe Cirrhosis
LSM 2.5– 7.0kPa à MildorabsentfibrosisislikelyLSM>12.5kPa à Cirrhosisislikely
2.5 7.0 9.5 12.5 12.5 kPa
Castera L, et al. J Hepatol. 2008;48(5):835-847
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Vibration Controlled Transient Elastography
Strengths• Potential for assessing hepatic
steatosis with CAP• Validated technology• Excellent at determining
advanced fibrosis and cirrhosis• Low sampling error
Limitations• Cut-off uncertain• Reduced accuracy in obese
patients• Limited availability
Kim, et. al. Radiology 2013; Adams, L. Non-invasive. Determination of Advanced Diseases in NAFLD. Web. 2017Copyright © 2018 by the AASLD
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Fibroscan results: Stiffness 8.1 kPa (F2), CAP score 253• Ultrasound of liver: no masses, hepatic steatosis • Change ART in anticipation of initiating HCV treatment
– Current ART: Elvitegravir/cobicistat//emtricitabine/tenofovir (TDF)– Not recommended with DAAs– Switch antiretrovirals to…
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
HIV/HCV Drug–Drug InteractionsARV(s) GLE/PIB GZR/EBR SOF/LDV SOF/VEL SOF/VEL/VOX
ATV + (RTV or COBI) X X ü* ü* X
DRV + (RTV or COBI) X X ü* ü* ü*†‡
LPV + RTV X X ü* ü* X
EFV X X ü* X X
RPV ü ü ü* ü ü
BIC ‒§ ‒§ ü† ü† ü†
DTG ü ü ü* ü ü
RAL ü ü ü ü ü
EVG/COBI/FTC/TDF ü*† X X ü* ü*†
EVG/COBI/FTC/TAF ü† X ü ü ü†
3TC/ABC ü ü ü ü ü
TAF or TDF ü ü ü* ü* ü*
DHHSGuidelines.2018.
*Monitorfortenofovir toxicityifusedwithTDF.‡Guidelinesrecommendmonitoringliverenzymesowingtolackofclinicalsafetydata
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Discussed care with PCP/HIV provider• Changed ART to dolutegravir/lamivudine/abacavir• 4 weeks later: Wait to assess tolerance and HIV suppression
– No complaints on new regimen– Tolerating without adverse effects– HIV RNA suppressed
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Factors to Consider in Selection of a DAA Regimen
• HCV genotype: determines selection of DAA …and insurance!
• Cirrhosis: duration of treatment
• Prior treatment experience (Interferon, Ribavirin, DAAs): Resistance testing
• Drug-drug interactions: statins, PPI, ART(boosted/TDF)
• Renal impairment: glecaprevir/pibrentasvir and elbasvir/grazoprevir can be used safely
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
• Switch ART to dolutegravir/lamivudine/abacavir • Initiated sofosbuvir/ledipisvir, on insurer’s formulary • Treat for 8 weeks or 12 weeks?
– HCV RNA 5.1 million IU/mL– African American – HIV +– Fibrosis stage F2
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
Regimens Not Recommended for Patients With HIV/HCV Coinfection
NOT RECOMMENDED RATING
Ledipasvir/sofosbuvir for 8 weeks is not recommended, regardless of baseline HCV RNA level.
IIb, C
www.hcvguidelines.org
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
AASLD/IDSA Recommendations for First-line HCV Treatment in HCV/HIV Coinfection
AASLD/IDSAHCVGuidelines.2018
*IfGT1awithBLNS5ARASsforEBR,12wks notrecommended;canincreasedurationto16wks withRBV(alternative).†Somedatatosupport8wks inGT1,but8wks notrecommendedinHCV/HIVcoinfection.‡Ifdecompensatedcirrhosis,donotuseHCVproteaseinhibitors.§IfBLY93HRASpresentinGT3,addRBVorconsiderSOF/VEL/VOX.‖Ifalsocirrhotic,increasedurationto12wks.
Duration,Wks NoCirrhosis CompensatedCirrhosis‡ eGFR <30mL/min
8 GLE/PIB – GLE/PIB‡‖
12 GZR/EBR,*SOF/LDV,† SOF/VEL
GLE/PIB,GZR/EBR,*SOF/LDV,SOF/VEL
GZR/EBR
8 GLE/PIB – GLE/PIB‡‖
12 SOF/VEL GLE/PIB,SOF/VEL§ –
8 GLE/PIB – GLE/PIB‡‖
12 SOF/LDV,SOF/VEL GLE/PIB,SOF/LDV,SOF/VEL
–
RegimenbyHCVGT
1,4
2,3
5,6
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Drug-Drug Interactions BetweenHCV Antivirals and Other Drugs
Drugs G/P GZR/EZR SOF/LED SOF/VEL SOF/VEL/VOX
Statins
Atorvastatin Max:20mg/d Monitor
Lovastatin Monitor
Simvastatin Monitor
Rosuvastatin Max:10mg/d Max:10mg/d statin;Avoid Max:10mg/d
PravastatinDecrease
pravastatin doseby50%
Monitor
Methadone
Proton pumpinhibitors
Canbetakentogether;Max:
omeprazole20mg/d
orequivalent
TakeDAAw/food4hrs beforePPI;Max:omeprazole20 mg/d
orequivalent
Avoidcoadministrationwhen possible.
Ifnecessary:TakeDAAw/food4hrs beforePPI;Max:omeprazole20
mg/dorequivalent
hcvguidelines.org
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a
Followupcare:Refertoendocrinologist,repeatultrasoundofliverin6months
WeekofTreatment Lab.Results(HCVRNAQuant
copies/mL)
ALT AST
Week 0- Baseline >5millioncopies/mL ALT96 AST205
Week4 464copies/mL ALT37 AST29
Week8 Notdetected - -
Week12 Notdetected - -
Week16 Notdetected - -
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
RiskFactorsAssociatedwithFasterFibrosisProgressioninChronicHCV
Poynard A. Antivir Ther. 2010;15(3):281-291;Poynard, et al. Lancet. 1997;349(9055):825-832.
HCC
DiseaseStateFactors Host/ViralFactors• Male gender • Age • Obesity• Diabetes• Metabolic
syndrome• Heavy alcohol consumption• Tobacco use
LifestyleFactors
• Fibrosis stage• Inflammation grade• Persistently elevated ALT
CirrhosisNormalLiver
• HIV, HBV co-infection• Immune system
compromise• Steatosis• Iron overload• Genotype 3
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
RiskofHBVReactivationinwithDAA’s• November2013– July2016:24casesofHBVReactivation
• Reactivationtypically4–8weeksafterHCVtreatmentinitiation• 2deaths,1livertransplant• BaselineHBVcharacteristics:
• 7HBsAg+andHBVDNA• 4HBsAg+undetectableHBVDNA• 3HBsAgandHBVDNAnegative;presumedisolatedcore+• 10HBVtestingnotreported/available
FDA. Drug Safety Communication. www.fda.gov/Drugs/DrugSafety/ucm522932.htm. Accessed 11/11/16.
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Hepatitis B and HCVHBsAg Anti-HBs HB core AB Meaning Action
- + - Prior vaccination with immunity
No HBV infection
- + + Prior HBV infection with immunity
Monitor during DAAs
+ - + Active HBV infection Consider HBV Rx concurrent with DAAs
- - + Isolated HBV core antibody, prior
infection, no immunity
Consider HBV DNAprior to DAAs for
“occult” HBV, monitor during DAAs
Hcvguidelines.org Version May 24, 2018
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Risk of HBV reactivation during HCV treatment:Suggestions for HBV Management/Monitoring
• sAg+ and detectable HBV DNA– HBV treatment initiated 4-6 weeks prior to HCV therapy
• sAg+, undetectable HBV DNA• Close monitoring (ALT/AST q2weeks; HBV DNA monthly)• Duration?
• Isolated core +, HBV DNA negative• Close monitoring• Double dose vaccine?FDA.DrugSafetyCommunication.www.fda.gov/Drugs/DrugSafety/ucm522932.htm.Accessed11/11/16
Slide courtesy of David L Wyles, MD.
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
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Harm Reduction
www.hcvguidelines.org
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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals
Take-Home Points…
• Liver fibrosis stage important pre-HCV therapy-Any method acceptableà just be sure to stage
• Consider drug-drug interactions with DAAs• DAAs efficacious, well tolerated in HIV/HCV
-genotype, cirrhosis, renal disease influence choice• Important to educate regarding reinfection
ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals