Retreatment for HCV may require switching DAA inhibitor classes

Patients who failed to achieve sustained virologic response after initial treatment for hepatitis C achieved high cure rates during retreatment after switching from an NS5A inhibitor direct-acting antiviral to a protease inhibitor.

“The management of DAA failure patients remains a challenge,” Julia Dietz, MD, from the Goethe University Hospital in Frankfurt, Germany, and colleagues wrote. They highlighted the fact that many patients develop resistance associated substitutions (RASs), particularly NS5A RASs, and there remains limited data on retreatment success.

To analyze the efficacy of retreatment with first generation DAAs, Dietz and colleagues reviewed data from 631 patients, 262 of whom completed retreatment.

Patients with genotype 1 initially received a combination of Sovaldi (sofosbuvir, Gilead Sciences) and an NS5A inhibitor, and those with genotype 3 underwent treatment with combination Daklinza (daclatasvir, Bristol-Myers Squibb) and sofosbuvir.

The SVR rates at follow-up were overall 84% among patients with genotype 1, 91% for those who received a regimen with sofosbuvir and a protease inhibitor, and 90% among those with RASs. Retreatment with a protease inhibitor without sofosbuvir was less effective with an SVR rate of 82%.

Repetition of treatment with sofosbuvir and an NS5A inhibitor without a protease inhibitor was comparatively ineffective with an SVR of 68%.

All patients with genotype 3 underwent retreatment with an NS5A inhibitor and sofosbuvir and 60% achieved SVR. Most of these patients had developed NS5A RASs (93%) and the SVR rates were higher in the absence of cirrhosis and Y93H.

“Interestingly, in a recent study with inclusion of a [protease inhibitor] ... the majority of treatment failures had [genotype 3],” Dietz and colleagues wrote, referring to Vosevi (sofosbuvir/velpatasvir/voxilaprevir, Gilead Sciences). “Thus, retreatment of [genotype 3] remains a challenge.” – by Talitha Bennett

Disclosures: Dietz reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.