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Resistance-associated substitutions and response to treatment in a chronic hepatitis C virus infected-patient: an unusual virological response case report.
Aldunate, Fabián; Echeverría, Natalia; Chiodi, Daniela; López, Pablo; Sánchez-Cicerón, Adriana; Soñora, Martín; Cristina, Juan; Moratorio, Gonzalo; Hernández, Nelia; Moreno, Pilar.
Afiliação
  • Aldunate F; Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, ZIP: 11400, Montevideo, Uruguay.
  • Echeverría N; Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Mataojo 2020, ZIP: 11400, Montevideo, Uruguay.
  • Chiodi D; Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, ZIP: 11400, Montevideo, Uruguay.
  • López P; Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Mataojo 2020, ZIP: 11400, Montevideo, Uruguay.
  • Sánchez-Cicerón A; Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Av. Italia s/n, ZIP: 11600, Montevideo, Uruguay.
  • Soñora M; Laboratorio de Patología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Av. Italia s/n, ZIP: 11600, Montevideo, Uruguay.
  • Cristina J; Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Av. Italia s/n, ZIP: 11600, Montevideo, Uruguay.
  • Moratorio G; Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, ZIP: 11400, Montevideo, Uruguay.
  • Hernández N; Laboratorio de Simulaciones Biomoleculares, Institut Pasteur de Montevideo, Mataojo 2020, ZIP: 11400, Montevideo, Uruguay.
  • Moreno P; Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, ZIP: 11400, Montevideo, Uruguay.
BMC Infect Dis ; 21(1): 387, 2021 Apr 26.
Article em En | MEDLINE | ID: mdl-33902462
BACKGROUND: Direct-Acting agents (DAAs) target and inhibit essential viral replication proteins. They have revolutionized the treatment of Hepatitis C virus (HCV) infection reaching high levels of sustained virologic response. However, the detection of basal resistance-associated substitutions (RASs) to DAAs in naïve patients could be important in predicting the treatment outcome in some patients exhibiting failures to DAA-based therapies. Therefore, the aim of this work was to evaluate the presence of RASs as minority variants within intra-host viral populations, and assess their relationship to response to therapy on a multiple times relapser patient infected chronically with HCV. CASE PRESENTATION: A male HCV infected-patient with a genotype 1a strain was evaluated. He had previously not responded to dual therapy (pegylated interferon-α plus ribavirin) and was going to start a direct-acting agent-based therapy (DAAs). He showed no significant liver fibrosis (F0). Viral RNA was extracted from serum samples taken prior and after therapy with DAAs (sofosbubir/ledipasvir/ribavirin). NS5A and NS5B genomic regions were PCR-amplified and the amplicons were sequenced using Sanger and next-generation sequencing (NGS) approaches. RASs were searched in in-silico translated sequences for all DAAs available and their frequencies were determined for those detected by NGS technology. Sanger sequencing did not reveal the presence of RASs in the consensus sequence neither before nor after the DAA treatment. However, several RASs were found at low frequencies, both before as well as after DAA treatment. RASs found as minority variants (particularly substitutions in position 93 within NS5A region) seem to have increased their frequency after DAA pressure. Nevertheless, these RASs did not become dominant and the patient still relapsed, despite perfect adherence to treatment and having no other complications beyond the infection (no significant fibrosis, no drug abuse). CONCLUSIONS: This report shows that some patients might relapse after a DAA-based therapy even when RASs (pre- and post-treatment) are detected in very low frequencies (< 1%) within intra-host viral populations. Increased awareness of this association may improve detection and guide towards a personalized HCV treatment, directly improving the outcome in hard-to-treat patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Ribavirina / Benzimidazóis / Hepacivirus / Hepatite C Crônica / Farmacorresistência Viral / Fluorenos / Sofosbuvir Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male / Middle aged Idioma: En Revista: BMC Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Ribavirina / Benzimidazóis / Hepacivirus / Hepatite C Crônica / Farmacorresistência Viral / Fluorenos / Sofosbuvir Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans / Male / Middle aged Idioma: En Revista: BMC Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Reino Unido