High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world

被引：13

作者：

Belen Perez, Ana ^{[1
]}

Chueca, Natalia ^{[2
]}

Garcia-Deltoro, Miguel ^{[3
]}

Maria Martinez-Sapina, Ana ^{[4
]}

Magdalena Lara-Perez, Maria ^{[5
]}

Garcia-Bujalance, Silvia ^{[6
]}

Aldamiz-Echevarria, Teresa ^{[7
]}

Jesus Vera-Mendez, Francisco ^{[8
]}

Antonio Pineda, Juan ^{[9
]}

Casado, Marta ^{[10
]}

Manuel Pascasio, Juan ^{[11
]}

Salmeron, Javier ^{[12
]}

Carlos Alados-Arboledas, Juan ^{[13
]}

Poyato, Antonio ^{[14
]}

Tellez, Francisco ^{[15
]}

Rivero-Juarez, Antonio ^{[16
]}

Merino, Dolores ^{[17
]}

Jesus Vivancos-Gallego, Maria ^{[18
]}

Miguel Rosales-Zabal, Jose ^{[19
]}

Garcia, Federico ^{[2
]}

Dolores Ocete, Maria ^{[20
]}

Angel Simon, Miguel ^{[21
]}

Rincon, Pilar ^{[9
]}

Reus, Sergi ^{[22
]}

De la Iglesia, Alberto ^{[23
]}

Garcia-Arata, Isabel ^{[24
]}

Jimenez, Miguel ^{[25
]}

Jimenez, Fernando ^{[26
]}

Hernandez-Quero, Jose ^{[27
]}

Galera, Carlos ^{[28
]}

Omar Balghata, Mohamed ^{[29
]}

Primo, Joaquin ^{[30
]}

Masia, Mar ^{[31
]}

Espinosa, Nuria ^{[32
]}

Delgado, Marcial ^{[33
]}

Angel von-Wichmann, Miguel ^{[34
]}

Collado, Antonio ^{[35
]}

Santos, Jesus ^{[36
]}

Minguez, Carlos ^{[37
]}

Diaz-Flores, Felicitas ^{[38
]}

Fernandez, Elisa ^{[39
]}

Bernal, Enrique ^{[40
]}

De Juan, Jose ^{[41
]}

Joaquin Anton, Jose ^{[42
]}

Velez, Monica ^{[43
]}

Aguilera, Antonio ^{[44
]}

Navarro, Daniel ^{[44
]}

Ignacio Arenas, Juan ^{[34
]}

Fernandez, Clotilde ^{[45
]}

Dolores Espinosa, Maria ^{[46
]}

机构：

[1] Univ Hosp Reina Sofia, Clin Microbiol Unit, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain

[2] Univ Hosp San Cecilio, Inst Invest Biosanit Ibs Granada, Clin Microbiol Unit, Granada, Spain

[3] Hosp Gen Valencia, Infect Dis Serv, Valencia, Spain

[4] Hosp Miguel Servet, Clin Microbiol Unit, Zaragoza, Spain

[5] Hosp Nuestra Senora de la Candelaria, Clin Microbiol Unit, Tenerife, Spain

[6] Univ Hosp La Paz, Clin Microbiol Unit, Madrid, Spain

[7] Hosp Gregorio Maranon, Infect Dis Unit, Madrid, Spain

[8] Univ Hosp Santa Lucia, Infect Dis Unit, Cartagena, Spain

[9] Univ Hosp Nuestra Senora de Valme, Infect Dis Unit, Seville, Spain

[10] Complejo Hosp Torrecardenas, Hepatol Unit, Almeria, Spain

[11] Univ Hosp Virgen del Rocio, Hepatol Unit, IBIS, CIBERehd, Seville, Spain

[12] Univ Hosp San Cecilio Granada, Inst Invest Biosanit Ibs Granada, Hepatol Unit, CIBERehd, Granada, Spain

[13] Univ Hosp Jerez, Clin Microbiol Unit, Cadiz, Spain

[14] Univ Hosp Reina Sofia, Hepatol Unit, Cordoba, Spain

[15] Hosp Puerto Real, Infect Dis Unit, Cadiz, Spain

[16] Univ Cordoba, Univ Hosp Reina Sofia, Infect Dis Unit, Inst Maimonides Invest Biomed Cordoba IMIBIC, Cordoba, Spain

[17] Univ Hosp Juan Ramon Jimenez, Infect Dis Unit, Huelva, Spain

[18] Univ Hosp Ramon y Cajal, Infect Dis Unit, Madrid, Spain

[19] Hosp Costa del Sol, Hepatol Unit, Malaga, Spain

[20] Hosp Gen Valencia, Clin Microbiol Unit, Valencia, Spain

[21] Hosp Miguel Servet, Hepatol Unit, Zaragoza, Spain

[22] Hosp Gen Alicante, Infect Dis Unit, Alicante, Spain

[23] Complejo Hosp Huelva, Clin Microbiol Unit, Huelva, Spain

[24] Hosp Univ Fuenlabrada, Clin Microbiol Unit, Madrid, Spain

[25] Hosp Reg Malaga, Hepatol Unit, Malaga, Spain

[26] Complejo Hosp Huelva, Hepatol Unit, Huelva, Spain

[27] Univ Hosp San Cecilio Granada, Infect Dis Unit, Granada, Spain

[28] Univ Hosp Virgen de la Arrixaca, Infect Dis Unit, Murcia, Spain

[29] Complejo Hosp Jaen, Infect Dis Unit, Jaen, Spain

[30] Hosp Sagunto, Hepatol Unit, Valencia, Spain

[31] Hosp Gen Elche, Infect Dis Unit, Alicante, Spain

[32] Univ Hosp Virgen del Rocio, Infect Dis Unit, Seville, Spain

[33] Hosp Reg Malaga, Infect Dis Unit, Malaga, Spain

[34] Univ Hosp Donostia, Infect Dis Unit, San Sebastian, Spain

[35] Complejo Hosp Torrecardenas, Infect Dis Unit, Almeria, Spain

[36] Univ Hosp Virgen de la Victoria, Infect Dis Unit, Malaga, Spain

[37] Castellon II Penitenciary Inst, Albocasser, Castellon De La, Spain

[38] Hosp Univ Canarias, Mol Diagnost Unit, Santa Cruz De Tenerife, Canary Islands, Spain

[39] Hosp Poniente, Infect Dis Unit, El Ejido, Almeria, Spain

[40] Hosp Gen Reina Sofia, Infect Dis Unit, Murcia, Spain

[41] Penitenciary Inst, Cordoba, Spain

[42] Penitenciary Inst, Granada, Spain

[43] Hosp Gen La Palma, Infect Dis Unit, Santa Cruz De Tenerife, Canary Islands, Spain

[44] Complejo Hosp Univ Santiago de Compostela, Clin Microbiol Unit, Santiago De Compostela, Spain

[45] Univ Hosp Puerta del Mar, Clin Microbiol Unit, Cadiz, Spain

[46] Univ Hosp Virgen de las Nieves, Hepatol Unit, Granada, Spain

[47] Univ Hosp Virgen Macarena, Infect Dis Unit, Seville, Spain

[48] Univ Hosp Gregorio Maranon, Clin Microbiol Unit, Madrid, Spain

[49] Univ Hosp Virgen de las Nieves, Infect Dis Unit, Granada, Spain

[50] Univ Hosp Torrevieja, Infect Dis Unit, Alicante, Spain

来源：

JOURNAL OF HEPATOLOGY | 2019年 / 71卷 / 05期

关键词：

HCV; RASs; Treatment failure; Resistance testing; Resistance-associated substitution; Direct-acting antivirals; Ribavirin; HEPATITIS-C VIRUS; GENOTYPE; ANTIVIRAL DRUGS; SUBSTITUTIONS; SOFOSBUVIR; INFECTION; THERAPY; LIFE; PREVALENCE; REGIMENS;

D O I：

10.1016/j.jhep.2019.06.022

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：876 / 888

页数：13

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