Treatment-naive Genotype 2 with Compensated Cirrhosis

Recommended and Alternative Regimens by evidence level and alphabetically for:

Genotype 2, Treatment-naive Patients, with Compensated Cirrhosis

RECOMMENDED DURATION RATING
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING
Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) 16 weeks to 24 weeks IIa, B
For decompensated cirrhosis, please refer to the appropriate section.
* The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4 inducers and inhibitors, respectively. Please refer to the prescribing information and the section on HIV/HCV coinfection for patients on antiretroviral therapy.

Sofosbuvir/velpatasvir

Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks was approved by the FDA for the treatment of HCV genotype 2 infection in patients with and without cirrhosis. ASTRAL-2 compared 12 weeks of sofosbuvir/velpatasvir to 12 weeks of sofosbuvir plus ribavirin in 266 treatment-naive and -experienced subjects with and without cirrhosis and showed superior efficacy (99% compared to 94%) (Foster, 2015a). ASTRAL-1 also included 104 genotype 2 treatment-naive and -experienced subjects with and without cirrhosis, all of whom achieved SVR12 (Feld, 2015). Pooled analysis of all genotype 2 subjects in ASTRAL-1 and -2, demonstrated 100% SVR12 in subjects with cirrhosis (29/29) and 99% SVR12 in naive subjects (194/195). Among patients with HCV genotype 2 receiving sofosbuvir/velpatasvir, the presence of baseline NS5A or NS5B resistance-associated substitutions was not associated with virologic failure.

Daclatasvir + sofosbuvir

Daclatasvir with sofosbuvir for 12 weeks was approved by the FDA for the treatment of HCV genotype 3 infection in patients without and with cirrhosis. Although daclatasvir with sofosbuvir was not approved for the treatment of HCV genotype 2 infection, daclatasvir maintains adequate activity against HCV genotype 2 despite a 50% effective concentration (EC50) that increases by several logs in the presence of the prevalent M31 substitution (Wang, 2014). In fact, daclatasvir with sofosbuvir was associated with high rates of SVR in treatment-naive patients with HCV genotype 2 infection with both 12 weeks and 24 weeks of therapy (Wyles, 2015); (Sulkowski, 2014a). It is unclear if there is a subgroup of HCV genotype 2-infected patients who would benefit from extending treatment. For patients who require treatment but cannot tolerate sofosbuvir/velpatasvir, a regimen of daclatasvir with sofosbuvir for 12 weeks is reasonable.

Last update: 
April 12, 2017

Additional Reading:    HIV/HCV Coinfection    Renal Impairment    Acute Infection

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