LAUSR

BACKGROUND Most hepatitis C virus (HCV) infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where Vosevi® may not be available. PATIENTS & METHODS GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response at 12 weeks after treatment completion (SVR12) was recorded. RESULTS A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) have been studied. After a resistance report, 186 patients were retreated. A SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after Paritaprevirritonavir+Ombitasvir±Dasabuvir ±ribavirin. CONCLUSIONS In our study we show how the resistance-guided retreatment in conjunction with an interpreted report allows achieving SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. LAY SUMMARY Currently, hepatitis C infection can be cured with the available antiviral agents. Despite a low proportion of patients fail to be cured; in absolute numbers, a high number of patients may need retreatment worldwide. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. The results of emerging resistance to the antiviral drugs used in the first treatment, in conjunction with an interpreted comprehensive report about these resistances allow us to show how retreatment efficacy with old drugs may be very close to the efficacy of the new drug combinations.