Summary: HCV Resistance Primer

Resistance Testing in Clinical Practice

Regimen-Specific Recommendations for Use of RAS Testing in Clinical Practice

RECOMMENDED RATING
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.
I, A
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.
I, A
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.
I, A
a Clinically important = ≥100-fold shift in the in vitro EC50 to ledipasvir

 

Table 1. Most Common, Clinically Important RASs by DAA, Genotype, and Fold Change
 

DAA Genotype 1a Genotype 1b Genotype 3a
M28T Q30R L31M/V Y93H/N L31V/I Y93H/N A30K Y93H
Ledipasvir 20x >100x >100x / >100x >1000x / >10,000x >100x >100x / -- NA NA
>50x
Elbasvir 20x >100x >10x >1000x / >1000x <10x >100x / -- 50x >100x
>100x
Velpatasvir <10x <3x 20x / 50x >100x / >1000x <3x <3x / -- 50x >100x
Pibrentasvir <3x <3x <3x <10x <3x <3x <3x <3x
Color Key: light green = <3-fold change; dark green = <10-fold change; orange = >10- to 100-fold change; pink = >100-fold change

 

Table 2. Clinically Important RASs by DAA Regimen and Genotype
 

DAA Regimen Genotype
1a 1b 3
Ledipasvir/sofosbuvir Q30H/R
L31M/V
Y93C/H/N
L31V
Y93H
NA
Elbasvir/grazoprevir M28A/T
Q30H/R
L31M/V
Y93C/H/N
Y93H NA
Sofosbuvir/velpatasvir NA NA Y93H

 

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 1b
TNa or TEb
1a
TN
1a
TE
No Cirrhosis
1a
TE
Cirrhosis
Ledipasvir/sofosbuvir No No Yes Yes
Elbasvir/grazoprevir No Yes Yes Yes
Sofosbuvir/velpatasvir No No No No
a TN = treatment naive
b TE = treatment experienced

 

Last update: 
November 6, 2019
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