Treatment of Chronic Hepatitis C After Sofosbuvir/Velpatasvir/Voxilaprevir or Sofosbuvir Plus Glecaprevir/Pibrentasvir Failure
This protocol applies to adults with chronic hepatitis C infection — either without cirrhosis or with compensated cirrhosis — whose prior therapy with sofosbuvir/velpatasvir/voxilaprevir, or with sofosbuvir plus glecaprevir/pibrentasvir, did not achieve virologic cure.
Failure on sofosbuvir/velpatasvir/voxilaprevir or on sofosbuvir plus glecaprevir/pibrentasvir substantially constrains retreatment options. The specific prior regimen that failed, the presence or absence of compensated cirrhosis, and HCV genotype all bear on the choice and duration of subsequent therapy.
Salvage therapy in this setting involves a combination of direct-acting antivirals, with regimen and duration tailored to the specific prior treatment failure and individual patient characteristics.
Sustained virologic response 12 weeks after completing therapy (SVR12) — confirmed undetectable HCV RNA — is the primary endpoint.
DOI: 10.1093/cid/ciad319
- Among patients with a prior sofosbuvir/velpatasvir/voxilaprevir treatment failure, 16 weeks of glecaprevir/pibrentasvir plus sofosbuvir and weight-based ribavirin is recommended based on the improved resistance profile of pibrentasvir and high response rate seen with this duration of therapy among genotype 3–infected participants in the MAGELLAN-3 trial.
- Extension to 24 wk should be considered in extremely difficult cases (eg, genotype 3 infection with compensated cirrhosis) or failure following sofosbuvir + glecaprevir/pibrentasvir therapy.
- A 24-week course of sofosbuvir/velpatasvir/voxilaprevir plus weight-based ribavirin is also recommended for persons with a prior sofosbuvir/velpatasvir/voxilaprevir treatment failure.
- SVR12, sustained virologic response 12 weeks after completion of therapy.