Successful Retreatment of Chronic HCV Genotype-1 Infection With Ledipasvir and Sofosbuvir After Initial Short Course Therapy With Direct-Acting Antiviral Regimens.
Clin Infect Dis
; 62(3): 280-288, 2016 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-26521268
ABSTRACT
BACKGROUND:
The optimal retreatment strategy for chronic hepatitis C virus (HCV) patients who fail directly-acting antiviral agent (DAA)-based treatment is unknown. In this study, we assessed the efficacy and safety of ledipasvir (LDV) and sofosbuvir (SOF) for 12 weeks in HCV genotype-1 (GT-1) patients who failed LDV/SOF-containing therapy.METHODS:
In this single-center, open-label, phase 2a trial, 34 participants with HCV (GT-1) and early-stage liver fibrosis who previously failed 4-6 weeks of LDV/SOF with GS-9669 and/or GS-9451 received LDV/SOF for 12 weeks. The primary endpoint was HCV viral load below the lower limit of quantification 12 weeks after completion of therapy (sustained virological response [SVR]12). Deep sequencing of the NS3, NS5A, and NS5B regions were performed at baseline, at initial relapse, prior to retreatment, and at second relapse with Illumina next-generation sequencing technology.RESULTS:
Thirty-two of 34 enrolled participants completed therapy. Two patients withdrew after day 0. Participants were predominantly male and black, with median baseline HCV viral load of 1.3 × 10(6) IU/mL and Metavir fibrosis stage 1 and genotype-1a. Median time from relapse to retreatment was 22 weeks. Prior to retreatment, 29 patients (85%) had NS5A-resistant variants. The SVR12 rate was 91% (31/34; intention to treat, ITT) after retreatment. One patient relapsed.CONCLUSIONS:
In patients who previously failed short-course combination DAA therapy, we demonstrate a high SVR rate in response to 12 weeks of LDV/SOF, even for patients with NS5A resistance-associated variants. CLINICAL TRIALS REGISTRATION NCT01805882.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Benzimidazóis
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Hepatite C Crônica
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Fluorenos
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Sofosbuvir
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Infect Dis
Assunto da revista:
DOENCAS TRANSMISSIVEIS
Ano de publicação:
2016
Tipo de documento:
Article