High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world
Por:
Belen Perez, Ana, Chueca, Natalia, Garcia-Deltoro, Miguel, Maria Martinez-Sapina, Ana, Magdalena Lara-Perez, Maria, Garcia-Bujalance, Silvia, Aldamiz-Echevarria, Teresa, Jesus Vera-Mendez, Francisco, Antonio Pineda, Juan, Casado, Marta, Manuel Pascasio, Juan, Salmeron, Javier, Carlos Alados-Arboledas, Juan, Poyato, Antonio, Tellez, Francisco, Rivero-Juarez, Antonio, Merino, Dolores, Jesus Vivancos-Gallego, Maria, Miguel Rosales-Zabal, Jose, Garcia, Federico, Dolores Ocete, Maria, Angel Simon, Miguel, Rincon, Pilar, Reus, Sergi, De la Iglesia, Alberto, Garcia-Arata, Isabel, Jimenez, Miguel, Jimenez, Fernando, Hernandez-Quero, Jose, Galera, Carlos, Omar Balghata, Mohamed, Primo, Joaquin, Masia, Mar, Espinosa, Nuria, Delgado, Marcial, Angel von-Wichmann, Miguel, Collado, Antonio, Santos, Jesus, Minguez, Carlos, Diaz-Flores, Felicitas, Fernandez, Elisa, Bernal, Enrique, De Juan, Jose, Joaquin Anton, Jose, Velez, Monica, Aguilera, Antonio, Navarro, Daniel, Ignacio Arenas, Juan, Fernandez, Clotilde, Dolores Espinosa, Maria, Rios, Maria Jose, Alonso, Roberto, Hidalgo, Carmen, Hernandez, Rosario, Jesus Tellez, Maria, Javier Rodriguez, Francisco, Antequera, Pedro, Delgado, Cristina, Martin, Patricia, Crespo, Javier, Becerril, Berta, Perez, Oscar, Garcia-Herola, Antonio, Montero, Jose, Freyre, Carolina, Grau, Concepcion
Publicada:
1 nov 2019
Resumen:
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
sofosbuvirtvelpatasvir/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 sofosbuvirtledipasvir +/- ribavirin (54%),
sofosbuvir/daclatasvir +/- ribavirin (23%), or paritaprevir-ritona
virtombitasvir +/- 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/ledi pasvir +/-
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. (C)
2019 European Association for the Study of the Liver. Published by
Elsevier B.V. All rights reserved.
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