Daclatasvir plus sofosbuvir

In the ALLY-3 study, treatment-experienced patients without cirrhosis did well with an SVR12 rate of 94% (32/34) (Nelson, 2015).

Sofosbuvir/velpatasvir

The phase III ASTRAL-3 study evaluated the fixed-dose combination of sofosbuvir/velpatasvir for 12 weeks without ribavirin in 277 genotype 3-infected patients, including 71 with prior treatment experience and 80 with cirrhosis (Foster, 2015a). Despite a high combined SVR12 rate of 95% (264/277), both prior treatment (90% SVR) and cirrhosis (91% SVR) had a moderate negative impact on treatment responses. The addition of ribavirin did appear to increase SVR12 rates in a phase II study of treatment-experienced genotype 3 patients treated for 12 weeks with 25 or 100 mg of velpatasvir combined with sofosbuvir (Pianko, 2015).

Baseline NS5A substitutions in genotype 3 also impact DAA treatment response, with the Y93H substitution being the most challenging. In the ALLY-3 study the Y93H was detected in 13 (9%) of patients with an SVR12 of 54% (7/13); including a 67% SVR12 in patients without cirrhosis. In the ASTRAL-3 study the Y93H was detected in 25 (9%) of patients with an SVR12 rate of 84% (21/25). Given that cirrhotic patients in whom prior treatment with PEG-IFN/ribavirin has failed are already recommended to have ribavirin added with or without extension of therapy depending on the specific regimen, baseline testing for NS5A RASs in genotype 3 would only impact treatment approaches for patients in whom prior treatment with PEG-IFN/ribavirin has failed without cirrhosis. Pending additional data, baseline NS5A RAS testing is recommended in all treatment-experienced genotype 3 patients without cirrhosis. If the Y93H substitution is identified, weight-based ribavirin should be added to the treatment course.