Findings from a study published in Hepatology support retreating patients with NS5A inhibitor failures with sofosbuvir + simeprevir. 

Sustained virologic response (SVR) failure with hepatitis C virus (HCV) direct-acting antiviral-based regimens is often linked to emergence of resistance-associated variants (RAVs). Recent guidelines recommend that patients who have failed treatment with NS5A inhibitors be retreated with sofosbuvir, an NS5B inhibitor, combined with simeprevir, a protease inhibitor. Supporting evidence on this, however, is inadequate. 

Researchers conducted a real-world study of 16 patients who had failed to achieve SVR on prior daclatasvir + peginterferon (pegIFN) and ribavirin, with or without asunaprevir, a protease inhibitor. They assessed antiviral efficacy using the primary endpoint of SVR 12, and on-treatment response was also assessed. Study patients were retreated for 12 weeks with sofosbuvir + simeprevir without ribavirin. 

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All patients achieved HCV RNA levels below lower limit of quantification (LLOQ) <12 IU/mL by end-of-treatment (EOT) and 10 out of 16 patients had a rapid response (Week 4). A total of 14 patients achieved SVR1 and the remaining 2 patients had relapsed by 4 weeks post-EOT. Study authors noted that simeprevir RAVs/polymorphisms at baseline did not predict retreatment failure.

In general, findings from the study support the recommendation of retreating NS5A failures with sofosbuvir + simeprevir. The most difficult-to-cure patients may require more than 12 weeks of retreatment and/or the addition of ribavirin, the authors added. 

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