2024-03-30T05:13:38Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2014182020-10-14T09:59:45Zcom_10261_11773com_10261_1col_10261_11774
00925njm 22002777a 4500
dc
Pérez, Ana Belén
author
Chueca, Natalia
author
García-Deltoro, Miguel
author
Martínez-Sapiñez, Ana María
author
Lara-Pérez, María Magdalena
author
García-Bujalance, Silvia
author
Aldámiz-Echevarría, Teresa
author
Vera-Méndez, Francisco Jesús
author
Pineda, Juan A.
author
Casado, Marta
author
Pascasio, Juan Manuel
author
Salmerón, Javier
author
Alados, Juan Carlos
author
Poyato, Antonio
author
Téllez, Francisco
author
Rivero-Juárez, Antonio
author
Merino, Dolores
author
Vivancos-Gallego, María Jesús
author
Rosales-Zábal, José Miguel
author
García, Federico
author
2019-11
[Background & Aims] 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 sofosbuvir/velpatasvir/voxilaprevir may not be available.
[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 (SVR) 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%) were studied. After a resistance report, 186 patients were retreated. An 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 paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin.
[Conclusions] In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve 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] Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.
Journal of Hepatology 71(5): 876-888 (2019)
http://hdl.handle.net/10261/201418
10.1016/j.jhep.2019.06.022
0168-8278
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100011011
HCV
RASs
Treatment failure
Resistance testing
Resistance-associated substitution
Direct-acting antivirals
Ribavirin
High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world