Regimens for chronic infection Gt 3 HCV
Genotype 3 HCV is harder to cure than Gt 1 or 2 HCV using DAA therapy, particularly in people with cirrhosis and prior non-responders to pegIFN plus ribavirin. The IFN-free treatment regimens available for prescription under the PBS for Gt 3 HCV include sofosbuvir plus velpatasvir for 12 weeks, sofosbuvir plus daclatasvir for 12 or 24 weeks, and sofosbuvir plus ribavirin for 24 weeks (Table 4).51,53,54 As of 1 November 2016, people with cirrhosis and Gt 3 HCV infection can be treated with sofosbuvir plus daclatasvir plus ribavirin for 12 weeks (compensated liver disease) or 24 weeks (decompensated liver disease). Ledipasvir is less effective against Gt 3 HCV, so is not recommended in this setting. Sofosbuvir is also available for prescription under the PBS in combination with pegIFN plus ribavirin as a 12-week treatment regimen.
Sofosbuvir plus velpatasvir
The combination of sofosbuvir plus velpatasvir is a safe and effective treatment for Gt 3 HCV (see section on Sofosbuvir plus velpatasvir and Table 4). The recommended treatment duration is 12 weeks for all patients. Cure rates > 95% were observed in clinical trials, including among people with cirrhosis.32 Patients with Gt 3 HCV who have cirrhosis and/or in whom treatment with pegIFN and ribavirin has previously failed have been observed to have slightly lower rates of SVR (89%–93%).32 For this group, consider adding ribavirin to the treatment regimen (Table 4).
Sofosbuvir plus daclatasvir, with or without ribavirin
Combination therapy with sofosbuvir and daclatasvir for 12 weeks in people with Gt 3 HCV infection and no cirrhosis is very effective, with SVR rates of 94%–97%.54 Lower SVR rates of 58%–69% are observed in those with cirrhosis, regardless of treatment history.54 Therefore, for people with Gt 3 HCV and cirrhosis, it is recommended that treatment be extended to 24 weeks (Table 4). Evidence supporting treatment extension comes from a French multicentre compassionate access program, which reported an SVR rate of 86% in patients with Gt 3 HCV infection and cirrhosis who were treated for 24 weeks with sofosbuvir plus daclatasvir.55 Recent data suggest that sofosbuvir plus daclatasvir plus ribavirin for 12 weeks may have similar efficacy in people with cirrhosis. The ALLY-3+ Study reported an overall SVR rate of 90% in people with advanced fibrosis or cirrhosis treated for 12 or 16 weeks with sofosbuvir plus daclatasvir plus ribavirin.56 The SVR rate in the cirrhosis subgroup was 86%. SVR rates were similar with 12 or 16 weeks’ treatment duration. The combination of sofosbuvir plus daclatasvir plus ribavirin for 12 weeks’ duration is now available on the PBS for the treatment of Gt 3 HCV in people with cirrhosis (Table 4). Treatment response rates for people with Gt 3 HCV, cirrhosis and decompensated liver disease remain suboptimal; in this population, the recommended treatment regimen is sofosbuvir plus daclatasvir plus ribavirin for 24 weeks (see Special populations: treatment of decompensated liver disease).
Sofosbuvir plus ribavirin
Sofosbuvir plus ribavirin combination therapy for 24 weeks is also PBS-approved for the treatment of Gt 3 HCV infection. In large Phase III studies, treatment with this regimen for 24 weeks achieved superior SVR rates to those with 12 or 16 weeks’ therapy.50,51 SVR rates after 24 weeks of sofosbuvir plus ribavirin are 90%–95% in treatment-naive people with no cirrhosis, and 58%–76% in treatment-experienced people with cirrhosis.51,52 In a head-to-head comparison, SVR rates were lower in people treated with sofosbuvir plus ribavirin for 24 weeks compared with sofosbuvir plus velpatasvir for 12 weeks.32 Thus, this is not the preferred regimen for people with Gt 3 HCV and cirrhosis, particularly those who are treatment-experienced.
Sofosbuvir plus peginterferon-alfa plus ribavirin
Data from a prospective, randomised Phase III trial demonstrate that triple therapy with sofosbuvir plus pegIFN plus ribavirin for 12 weeks is very effective for the treatment of Gt 3 HCV. This regimen is more effective than 16 or 24 weeks of sofosbuvir plus ribavirin, including among treatment-experienced people with cirrhosis, but it is associated with pegIFNrelated toxicity.52 This triple regimen is likely to be most useful as salvage therapy for the minority of people with Gt 3 HCV in whom first-line DAAs fail, although effective triple DAA therapy is now in development for this group (Table 4).