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Advances in Hepatitis C Virus Treatment
for HIV-Infected Persons: Have We
Reached the End of the Rainbow?
Kara W. Chew, MD, MS
Assistant Clinical Professor of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California
FLOWED: 04/18/2016
Los Angeles, California: April 25, 2016
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Learning Objectives
After attending this presentation, participants will
be able to:
 Conduct the initial evaluation for hepatitis C virus
(HCV) including hepatic fibrosis assessment
 Select between treatment options for genotype 1
HCV in HIV/HCV-coinfected patients
 List treatment options for genotype 2, 3, or 4
HCV infection
Slide 2 of 9
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Evaluation for advanced fibrosis is recommended for all
 Necessary to determine the appropriate HCV treatment strategy
–
–
Impacts treatment options
Depending on the genotype and regimen:
 Treatment
duration may need to be extended
 Addition of ribavirin may need to be considered
 Additional management necessary for advanced fibrosis/cirrhosis
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–
–
–
Screening for hepatocellular carcinoma
Screening for esophageal varices
Monitoring of hepatic function
Counseling to avoid NSAIDs, limit acetaminophen use, avoid raw
shellfish
Slide 3 of 9
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Recommended approach for fibrosis assessment
• Combining direct biomarkers and transient elastography is
most efficient
•
If discordant, consider liver biopsy
• If direct biomarkers or transient elastography not available,
combine indirect serum biomarkers
•
If indeterminate, consider liver biopsy
AASLD/IDSA, hcvguidelines.org, Boursier Hepatology 2012
Slide 4 of 9
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Key considerations when choosing between
HCV treatment regimens
 Drug interactions between ART and HCV DAAs
 Drug interactions between HCV DAAs and drugs for comorbidities
– E.g. PPIs, statins, anticonvulsants, dihydropyridines, rifampin, digoxin
 Comorbidities:
– Cardiac disease (anemia with RBV, drug interactions with cardiac meds)
– Renal insufficiency (limited data for most DAAs with advanced kidney
disease/ESRD, increased tenofovir levels with coadministration of ledipasvir
with TDF)
Slide 5 of 9
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Drug-drug interactions between ART and HCV treatment
HCV regimen
Allowed ART
Comments
Ledipasvir/sofosbuvir Most ART allowed
(LDV/SOF)
Interaction between ledipasvir and
TDF, ledipasvir and cobicistat
LDV increases tenofovir levels – avoid
coadmin with TDF if CrCL <60 mL/min and
avoid LDV + TDF with ritonavir- or
cobicistat-boosted ART
Elbasvir/grazoprevir
Raltegravir, dolutegravir, rilpivirine,
tenofovir, abacavir, emtricitabine,
enfuvirtide, lamivudine,
NO HIV-1 protease inhibitors or efavirenz
Paritaprevir/ritonavir/
ombitasvir +
dasabuvir
Atazanavir, dolutegravir, raltegravir,
emtricitabine, lamivudine, tenofovir,
enfuvirtide
NO efavirenz
If ritonavir in ART regimen, hold ritonavir in
ART for dose due with HCV treatment
Simeprevir
Raltegravir, (dolutegravir), rilpivirine,
maraviroc, abacavir, emtricitabine,
tenofovir, lamivudine, enfuvirtide
NO HIV-1 protease inhibitors or efavirenz
Daclatasvir (DCV)
-Note standard DCV
dose
is 60 mg
Slide 6 of 9
No restrictions
Dose adjustment with select ART
DCV dose to 30 mg with r/ATV, IDV, NFV,
SQV, cobi-containing ART (except DRVcobi).  DCV dose to 90 mg with efavirenz,
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
etravirine, nevirapine
Treatment recommendations - HCV genotype 3
Treatment naïve
and PEG-IFN/RBV
experienced noncirrhotic
Treatment naïve
compensated
cirrhotic
PEG-IFN/RBV
treatment
experienced
compensated
cirrhotic
Sofosbuvir + WBR
+ PEG-IFN x 12
weeks (IA)
Sofosbuvir/RBV
experienced noncirrhotic or
cirrhotic
Daclatasvir +
sofosbuvir x 12
weeks (IA)
Sofosbuvir + WBR
+ PEG-IFN x 12
weeks (IA)
Sofosbuvir + WBR
+ PEG-IFN x 12
weeks (IA)
Daclatasvir +
Daclatasvir +
Daclatasvir +
sofosbuvir +/- WBR sofosbuvir + WBR x sofosbuvir + WBR x
x 24 weeks (IIaB)
24 weeks (IIaB)
24 weeks (IIaC)
Sofosbuvir + WBR
+ PEG-IFN x 12
weeks (IIaC)
WBR = weight-based ribavirin, RBV = ribavirin; Strength of recommendation provided by Class (I, IIa/b, III)
AASLD/IDSA HCV Guidance
and Level (A, B, C), PEG-IFN= pegylated interferon
Slide 7 of 9
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Determining treatment response and
post-treatment follow-up
 Quantitative HCV RNA at week 4 on treatment and 12 weeks after
treatment completion (SVR12 determination)
 Can consider HCV RNA at end of treatment and 24 weeks after end
of treatment (SVR24)
–
>99% concordance between SVR12 and SVR24
 Remind patients that treatment cure does not = HCV immunity
 High rates of reinfection in HIV/HCV co-infected persons
–
–
HIV+ MSM without IDU, 2-year cumulative reinfection rates 25-33%
Continue to review risk factors
 Ongoing cirrhosis/chronic liver disease management
Slide 8 of 9
Yoshida et al, Hepatology 2015, Martin et al, AIDS 2013, Lambers et al, AIDS 2011, AASLD/IDSA HCV guidance
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.
Management of treatment failures
 Optimal retreatment strategy unknown
 If urgent to retreat:
Resistance testing for NS3 and NS5A resistance mutations
– Include RBV on retreatment
– Consider PEG-IFN
– Consider a clinical trial
–
AASLD/IDSA HCV Guidance, hcvguidelines.org
Slide 9 of 9
From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.

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