Summary: HCV Resistance Primer
Resistance Testing in Clinical Practice
Regimen-Specific Recommendations for Use of RAS Testing in Clinical Practice
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RECOMMENDED
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RATING
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Elbasvir/grazoprevir
NS5A RAS testing is recommended for genotype 1a-infected, treatment-naive or -experienced patients being considered for elbasvir/grazoprevir. If present, a different regimen should be considered.
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I, A
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Ledipasvir/sofosbuvir
NS5A RAS testing can be considered for genotype 1a-infected, treatment-experienced patients with and without cirrhosis being considered for ledipasvir/sofosbuvir. If clinically importanta resistance is present, a different recommended therapy should be used.
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I, A
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Sofosbuvir/velpatasvir
NS5A RAS testing is recommended for genotype 3-infected, treatment-naive patients with cirrhosis and treatment-experienced patients (without cirrhosis) being considered for 12 weeks of sofosbuvir/velpatasvir. If Y93H is present, weight-based ribavirin should be added or another recommended regimen should be used.
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I, A
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a Clinically important = ≥100-fold shift in the in vitro EC50 to ledipasvir
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Table 1. Most Common, Clinically Important RASs by DAA, Genotype, and Fold Change
DAA
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Genotype 1a
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Genotype 1b
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Genotype 3a
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M28T
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Q30R
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L31M/V
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Y93H/N
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L31V/I
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Y93H/N
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A30K
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Y93H
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Ledipasvir
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20x
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>100x
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>100x / >100x
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>1000x / >10,000x
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>100x
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>100x / --
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NA
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NA
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>50x
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Elbasvir
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20x
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>100x
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>10x
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>1000x / >1000x
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<10x
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>100x / --
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50x
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>100x
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>100x
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Velpatasvir
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<10x
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<3x
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20x / 50x
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>100x / >1000x
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<3x
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<3x / --
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50x
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>100x
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Pibrentasvir
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<3x
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<3x
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<3x
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<10x
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<3x
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<3x
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<3x
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<3x
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Color Key: light green = <3-fold change; dark green = <10-fold change; orange = >10- to 100-fold change; pink = >100-fold change
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Table 2. Clinically Important RASs by DAA Regimen and Genotype
DAA Regimen
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Genotype
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1a
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1b
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3
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Ledipasvir/sofosbuvir
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Q30H/R
L31M/V
Y93C/H/N
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L31V
Y93H
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NA
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Elbasvir/grazoprevir
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M28A/T
Q30H/R
L31M/V
Y93C/H/N
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Y93H
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NA
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Sofosbuvir/velpatasvir
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NA
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NA
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Y93H
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Glecaprevir/pibrentasvir
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NA
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NA
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A30K
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Table 3. NS5A RAS Testing Recommendations Prior to Initiation of DAA Treatment Among Genotype 1 Patients by DAA Regimen, Virus Subtype, Prior Treatment Status, and Cirrhosis Status
DAA Regimen
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1b
TNa or TEb
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1a
TN
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1a
TE
No Cirrhosis
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1a
TE
Cirrhosis
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3
TN
Cirrhosis
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3
TE
No Cirrhosis
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Ledipasvir/sofosbuvir
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No
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No
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Yes
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Yes
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N/A
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N/A
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Elbasvir/grazoprevir
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No
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Yes
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Yes
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Yes
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N/A
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N/A
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Sofosbuvir/velpatasvir
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No
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No
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No
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No
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Yes
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Yes
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Glecaprevir/pibrentasvir
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No
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No
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No
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No
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No
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No
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a TN = treatment naive
b TE = treatment experienced
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