Monday, March 31, 2014

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.

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

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. (

PubMed abstract (Free) - See more

No comments:

Post a Comment