High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.
Por:
Perez, A, Chueca, N, Garcia-Deltoro, M, Martinez-Sapina, A, Lara-Perez, M, Garcia-Bujalance, S, Aldamiz-Echevarria, T, Vera-Mendez, F, Pineda, J, Casado, M, Pascasio, J, Salmeron, J, Alados-Arboledas, J, Poyato, A, Tellez, F, Rivero-Juarez, A, Merino, D, Vivancos-Gallego, M, Rosales-Zabal, J, Garcia, F, Ocete, M, Simon, M, Rincon, P, Reus S, De la Iglesia, A, Garcia-Arata, I, Jimenez, M, Jimenez, F, Hernandez-Quero, J, Galera, C, Balghata, M, Primo, J, Masia, M, Espinosa, N, Delgado, M, von-Wichmann, M, Collado, A, Santos, J, Minguez, C, Diaz-Flores, F, Fernandez, E, Bernal, E, De Juan, J, Anton, J, Velez, M, Aguilera, A, Navarro, D, Arenas, J, Fernandez, C, Espinosa, M, Rios, M, Alonso, R, Hidalgo, C, Hernandez, R, Tellez, M, Rodriguez, F, Antequera, P, Delgado, C, Martin, P, Crespo, J, Becerril, B, Perez, O, Garcia-Herola, A, Montero, J, Freyre, C and Grau, C
Publicada:
1 nov 2019
Ahead of Print:
4 jul 2019
Categoría:
Hepatology
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 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.
Filiaciones:
Perez, A:
Univ Hosp Reina Sofia, Clin Microbiol Unit, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain
Chueca, N:
Univ Hosp San Cecilio, Inst Invest Biosanit Ibs Granada, Clin Microbiol Unit, Granada, Spain
Garcia-Deltoro, M:
Hosp Gen Valencia, Infect Dis Serv, Valencia, Spain
Martinez-Sapina, A:
Hosp Miguel Servet, Clin Microbiol Unit, Zaragoza, Spain
Lara-Perez, M:
Hosp Nuestra Senora de la Candelaria, Clin Microbiol Unit, Tenerife, Spain
Garcia-Bujalance, S:
Univ Hosp La Paz, Clin Microbiol Unit, Madrid, Spain
Aldamiz-Echevarria, T:
Hosp Gregorio Maranon, Infect Dis Unit, Madrid, Spain
Vera-Mendez, F:
Univ Hosp Santa Lucia, Infect Dis Unit, Cartagena, Spain
Pineda, J:
Univ Hosp Nuestra Senora de Valme, Infect Dis Unit, Seville, Spain
Casado, M:
Complejo Hosp Torrecardenas, Hepatol Unit, Almeria, Spain
Pascasio, J:
Univ Hosp Virgen del Rocio, Hepatol Unit, IBIS, CIBERehd, Seville, Spain
Salmeron, J:
Univ Hosp San Cecilio Granada, Inst Invest Biosanit Ibs Granada, Hepatol Unit, CIBERehd, Granada, Spain
Alados-Arboledas, J:
Univ Hosp Jerez, Clin Microbiol Unit, Cadiz, Spain
Poyato, A:
Univ Hosp Reina Sofia, Hepatol Unit, Cordoba, Spain
Tellez, F:
Hosp Puerto Real, Infect Dis Unit, Cadiz, Spain
Rivero-Juarez, A:
Univ Cordoba, Univ Hosp Reina Sofia, Infect Dis Unit, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain
Merino, D:
Univ Hosp Juan Ramon Jimenez, Infect Dis Unit, Huelva, Spain
Vivancos-Gallego, M:
Univ Hosp Ramon y Cajal, Infect Dis Unit, Madrid, Spain
Rosales-Zabal, J:
Hosp Costa del Sol, Hepatol Unit, Malaga, Spain
Garcia, F:
Univ Hosp San Cecilio, Inst Invest Biosanit Ibs Granada, Clin Microbiol Unit, Granada, Spain
Ocete, M:
Hosp Gen Valencia, Clin Microbiol Unit, Valencia, Spain
Simon, M:
Hosp Miguel Servet, Hepatol Unit, Zaragoza, Spain
Rincon, P:
Univ Hosp Nuestra Senora de Valme, Infect Dis Unit, Seville, Spain
Reus S:
Hosp Gen Alicante, Infect Dis Unit, Alicante, Spain
De la Iglesia, A:
Complejo Hosp Huelva, Clin Microbiol Unit, Huelva, Spain
Garcia-Arata, I:
Hosp Univ Fuenlabrada, Clin Microbiol Unit, Madrid, Spain
Jimenez, M:
Hosp Reg Malaga, Hepatol Unit, Malaga, Spain
Jimenez, F:
Complejo Hosp Huelva, Hepatol Unit, Huelva, Spain
Hernandez-Quero, J:
Univ Hosp San Cecilio Granada, Infect Dis Unit, Granada, Spain
Galera, C:
Univ Hosp Virgen de la Arrixaca, Infect Dis Unit, Murcia, Spain
Balghata, M:
Complejo Hosp Jaen, Infect Dis Unit, Jaen, Spain
:
Hosp Sagunto, Hepatol Unit, Valencia, Spain
:
Hosp Gen Elche, Infect Dis Unit, Alicante, Spain
Espinosa, N:
Univ Hosp Virgen del Rocio, Infect Dis Unit, Seville, Spain
Delgado, M:
Hosp Reg Malaga, Infect Dis Unit, Malaga, Spain
von-Wichmann, M:
Univ Hosp Donostia, Infect Dis Unit, San Sebastian, Spain
Collado, A:
Complejo Hosp Torrecardenas, Infect Dis Unit, Almeria, Spain
Santos, J:
Univ Hosp Virgen de la Victoria, Infect Dis Unit, Malaga, Spain
:
Castellon II Penitenciary Inst, Albocasser, Castellon De La, Spain
Diaz-Flores, F:
Hosp Univ Canarias, Mol Diagnost Unit, Santa Cruz De Tenerife, Canary Islands, Spain
Fernandez, E:
Hosp Poniente, Infect Dis Unit, El Ejido, Almeria, Spain
Bernal, E:
Hosp Gen Reina Sofia, Infect Dis Unit, Murcia, Spain
De Juan, J:
Penitenciary Inst, Cordoba, Spain
Anton, J:
Penitenciary Inst, Granada, Spain
Velez, M:
Hosp Gen La Palma, Infect Dis Unit, Santa Cruz De Tenerife, Canary Islands, Spain
Aguilera, A:
Complejo Hosp Univ Santiago de Compostela, Clin Microbiol Unit, Santiago De Compostela, Spain
Navarro, D:
Complejo Hosp Univ Santiago de Compostela, Clin Microbiol Unit, Santiago De Compostela, Spain
Arenas, J:
Univ Hosp Donostia, Infect Dis Unit, San Sebastian, Spain
Fernandez, C:
Univ Hosp Puerta del Mar, Clin Microbiol Unit, Cadiz, Spain
Espinosa, M:
Univ Hosp Virgen de las Nieves, Hepatol Unit, Granada, Spain
Rios, M:
Univ Hosp Virgen Macarena, Infect Dis Unit, Seville, Spain
Alonso, R:
Univ Hosp Gregorio Maranon, Clin Microbiol Unit, Madrid, Spain
Hidalgo, C:
Univ Hosp Virgen de las Nieves, Infect Dis Unit, Granada, Spain
:
Univ Hosp Torrevieja, Infect Dis Unit, Alicante, Spain
Tellez, M:
Hosp Clin San Carlos, Infect Dis Unit, Madrid, Spain
Rodriguez, F:
Hosp Gen Reina Sofia, Hepatol Unit, Murcia, Spain
Antequera, P:
Univ Hosp Jose Maria Morales Meseguer, Clin Microbiol Unit, Murcia, Spain
Delgado, C:
Hosp Alto Guadalquivir, Infect Dis Unit, Jaen, Spain
Martin, P:
Hosp Denia, Internal Med Unit, Alicante, Spain
Crespo, J:
Univ Hosp Marques de Valdecilla, Hepatol Unit, Santander, Spain
Becerril, B:
Hosp Punta de Europa, Clin Microbiol Unit, Cadiz, Spain
Perez, O:
Hosp Castellon de la Plana, Clin Microbiol Unit, Castellon De La Plana, Spain
:
Hosp Marina Baixa, Hepatol Unit, Alicante, Spain
Montero, J:
Univ Hosp Puerto Real, Hepatol Unit, Cadiz, Spain
Freyre, C:
Univ Hosp Puerto Real, Clin Microbiol Unit, Cadiz, Spain
:
Hosp Vega Baja, Hepatol Unit, Alicante, Spain
Open Access
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