High efficacy of HCV resistance-guided retreatment strategies after protease inhibitors failure in real-life settings

Valeria Cento

Background: In clinical studies, patients who failed first-generation protease inhibitors (PIs) are retreated with PI-free regimens, but real-life practice can be quite different. We analyzed the efficacy of various interferon (IFN)-free regimens after PI failure, and the role of natural and acquired resistance associated substitutions (RASs) in real-life settings.
Main Results: In this multicenter, observational study, 74 patients with chronic HCV infection (84% cirrhotic) were retreated after a PI plus pegIFN and ribavirin (RBV) failure. RASs testing by Sanger sequencing was evaluated in only few cases prior to start 2nd line treatment, affecting the rate of sustained viral response (SVR). Indeed, following AASLD/EASL recommendations, 31 patients started a 2nd line regimen of sofosbuvir plus an NS5A-inhibitor and RBV, without prior NS5A RAS testing. The SVR rate was 91% (28/31), lower that the 100% SVR observed in 13 patients who started a NS3- or NS5A-containing regimen chosen by baseline RASs testing. The 30 patients who received a not-recommended, not RASs-guided regimen had the lowest SVR rate (76%; p-trend=0.086), including those retreated with sofosbuvir+RBV (SVR=43%). NS5A or NS3 failure was associated with an increase of RASs, respecting to baseline.
Conclusions: Proper planning of 2nd line regimens, chosen by RASs evaluation, may allow optimization of response rates, and avoid the generation of highly-resistant and potentially incurable viral strains.

Anna Scotti
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