Sofosbuvir plus a Second Antiviral for HCV Genotype 1 Infection?

Sofosbuvir plus a Second Antiviral for HCV Genotype 1 Infection?
Atif Zaman, MD, MPH reviewing Gane EJ et al. Gastroenterology 2014.

Atif Zaman, MD, MPH

Preliminary data show promising results for interferon-free regimens with ledipasvir and GS-9669, even among patients with cirrhosis and prior null response.

Atif Zaman, MD, MPH

Sofosbuvir-based regimens are currently approved for the treatment of hepatitis C virus (HCV) infection. However, the most effective sofosbuvir-based regimens for genotype 1 infection still include interferon, and few data are available regarding the efficacy in treatment-experienced patients.

To test the safety and efficacy of two interferon-free, sofosbuvir-based regimens in patients with HCV genotype 1 infection, researchers enrolled 113 patients (including 38 prior null responders and 19 with cirrhosis) to receive sofosbuvir (400 mg daily) and ledipasvir (90 mg daily) plus ribavirin (1000–1200 mg daily) for 6 weeks or 12 weeks, or sofosbuvir and GS-9669 (500 mg daily) plus ribavirin for 12 weeks. The primary endpoint was sustained virologic response (SVR) at 12 weeks posttreatment.

Results are as follows:
In treatment-naive patients, the SVR rate was 100% (25 of 25) for the 12-week regimen of sofosbuvir, ledipasvir, and ribavirin; 68% (17 of 25) for the 6-week regimen; and 92% (23 of 25) for the regimen of sofosbuvir, GS-9669, and ribavirin.

Among prior null responders without cirrhosis, the SVR rate was 100% for both regimens (a total of 19 patients).

Prior null responders with cirrhosis received sofosbuvir and ledipasvir with and without ribavirin, and respective SVR rates were 100% (9 of 9) and 70% (7 of 10).

Side effects were mild and included headache, fatigue, and nausea.

Comment
The findings of this small, early study demonstrate that interferon-free, sofosbuvir-based regimens will likely be effective in patients with HCV genotype 1 infection, even those with cirrhosis and prior null response. However, they also suggest that a very short course of therapy such as 6 weeks may be inadequate, and for the most difficult-to-treat subgroups, ribavirin will likely still be needed.

Editor Disclosures at Time of Publication

Citation(s):
Gane EJ et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology 2014; 146:736. (http://dx.doi.org/10.1053/j.gastro.2013.11.007)

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