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 without cirrhosis being considered for ledipasvir/sofosbuvir. If clinically importanta resistance is present, a different recommended therapy should be used.

NS5A RAS testing can be considered for genotype 1a-infected, treatment-experienced patients with 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 (with or without cirrhosis) being considered for 12 weeks of sofosbuvir/velpatasvir. If Y93H is present, weight-based ribavirin should be added or sofosbuvir/velpatasvir/voxilaprevir should be used.
I, A

Daclatasvir plus sofosbuvir

NS5A RAS testing is recommended for genotype 3-infected, treatment-experienced patients without cirrhosis being considered for 12 weeks of daclatasvir plus sofosbuvir. If Y93H is present, weight-based ribavirin should be added.

NS5A RAS testing is recommended for genotype 3-infected, treatment-naive patients with cirrhosis being considered for 24 weeks of daclatasvir plus sofosbuvir. If Y93H is present, treatment should include weight-based ribavirin, or a different recommended therapy used.

I, B
a Clinically important = greater than 100-fold resistance

 

 

Regimen-Specific Clinical Practice Situations in Which RAS Testing Is Not Recommended

NOT RECOMMENDED RATING

Elbasvir/grazoprevir

RAS testing is not recommended for any genotype 1b-infected patients being considered for elbasvir/grazoprevir therapy.
I, A

Glecaprevir/pibrentasvir

RAS testing is not recommended for patients with genotype 1, 2, 3, 4, 5, or 6 infection being considered for glecaprevir/pibrentasvir for 8, 12, or 16 weeks.
I, A

Ledipasvir/sofosbuvir

NS5A RAS testing is not recommended for any genotype 1b-infected patients being considered for ledipasvir/sofosbuvir therapy.

I, A

NS5A RAS testing is not recommended for genotype 1a-infected, treatment-naive patients being considered for ledipasvir/sofosbuvir therapy.

I, A 
NS5A RAS testing is not recommended for genotype 1a- or 1b-infected, treatment-naive patients without cirrhosis and with a viral load <6 million IU/mL being considered for an 8-week course of ledipasvir/sofosbuvir therapy. I, A

Paritaprevir/ritonavir/ombitasvir with dasabuvir ± weight-based ribavirin, or paritaprevir/ritonavir/ombitasvir + weight-based ribavirin

RAS testing is not recommended for genotype 1- or 4-infected, treatment-naive or -experienced patients being considered for therapy with paritaprevir/ritonavir/ombitasvir with dasabuvir ± weight-based ribavirin or paritaprevir/ritonavir/ombitasvir + weight-based ribavirin, respectively.
I, A

Sofosbuvir/velpatasvir

RAS testing is not recommended for patients with genotype 1, 2, 4, 5, or 6 infection being considered for 12 weeks of sofosbuvir/velpatasvir therapy.
I, A

Sofosbuvir/velpatasvir/voxilaprevir

RAS testing is not recommended for patients with genotype 1, 2, 3, 4, 5, or 6 infection being considered for 12 weeks of sofosbuvir/velpatasvir/voxilaprevir therapy.
I, A

 

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

DAA Genotype 1a Genotype 1b
M28T Q30R L31M/V Y93H/N L31V/I Y93H/N
Ledipasvir 20x >100x >100x / >100x >1000x / >10,000 >100x/ >100x / --
>50x
Ombitasvir >1000x >100x <3x >10,000x / >10,000x <10x 20x / 50x
>100x
Daclatasvir >100x >1000x >100x / >1000x >1000x / >10,000x <10x 20x / 50x
Elbasvir 20x >100x >10x >1000x / >1000x <10x >100x / --
>100x
Velpatasvir <10x <3x 20x / 50x >100x/ >1000x <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
n/a
Elbasvir/grazoprevir M28A/T
Q30H/R
L31M/V
Y93C/H/N
Y93H n/a
Paritaprevir/ritonavir/ombitasvir with dasabuvir ± ribavirin n/a n/a n/a
Sofosbuvir/velpatasvir n/a n/a Y93H

 

Table 3. NS5A RAS Testing Recommendations Prior to Initiation of DAA Treatment Among Genotype 1 Patients by DAA Regimen, Virus Subtype, Prior Treatment Experience, 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
Paritaprevir/ritonavir/ombitasvir with dasabuvir ± ribavirin No No No No
a TN = treatment naive
b TE = treatment experienced

 

Last update: 
May 24, 2018
Top