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Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy.

ABSTRACT: We report the case of a 45-year-old haemodialysis patient who achieved a sustained virological response (SVR) following pegylated interferon therapy for hepatitis C virus (HCV) genotype 2 infection. He was subsequently cohorted with other HCV-infected dialysis patients and became re-infected with HCV genotype 3a. Epidemiological and molecular investigations identified a highly viraemic HCV genotype 3a-infected dialysis patient as the likely source of this infection. This critical incident informed a revision to local and national infection control policy regarding the dialysis management of patients who achieve an SVR following anti-viral treatment.

SUBMITTER: O'Shaughnessy MM

PROVIDER: S-EPMC4400513 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy.

O'Shaughnessy Michelle M MM O'Regan John A JA Murray Frank E FE Connell Jeff A JA Duffy Margaret P MP Francis Veronica M VM Dwyer Sharon S Thornton Lelia M LM Conlon Peter J PJ

Clinical kidney journal 20120418 3

We report the case of a 45-year-old haemodialysis patient who achieved a sustained virological response (SVR) following pegylated interferon therapy for hepatitis C virus (HCV) genotype 2 infection. He was subsequently cohorted with other HCV-infected dialysis patients and became re-infected with HCV genotype 3a. Epidemiological and molecular investigations identified a highly viraemic HCV genotype 3a-infected dialysis patient as the likely source of this infection. This critical incident inform ...[more]

PMID: 26069778

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Project description:Background:The efficacy of direct-acting antivirals (DAAs) depends on the hepatitis C virus (HCV) genotype 4 (GT4) subtype which are used in the treatment of HCV. We aimed to retrospectively investigate the baseline prevalence of HCV NS5A and NS5B polymorphisms and their impact on virological outcome in GT4-infected patients treated with various DAA regimens. Patients and methods:Available plasma samples from HCV GT4-infected patients treated with different DAA regimens were analyzed at baseline and after treatment failure, where applicable. Sanger sequencing of patient-derived NS5A and NS5B regions was performed on all available samples, while ultradeep pyrosequencing (UDPS) of NS5A and NS5B regions was performed only on samples from treatment failures at different time points. Results:Sustained virological response (SVR) was achieved by 96% (48/50) of patients. Of 16 patients with baseline NS5A sequence, polymorphisms at amino acid positions associated with drug resistance were detected only at position 58: P58 (69.2%) and T58 (30.8%). Of 21 patients with baseline NS5B sequence, N142S was detected only in the two treatment failures, both with GT4d were treated with sofosbuvir (SOF)-based regimens, suggesting a potential involvement in SOF efficacy. Two patients (patient 1 [Pt1] and patient 2 [Pt2]) relapsed. In Pt1, NS5A-T56I and NS5A-Y93H/S emerged. In Pt2, NS5A-L28F emerged and a novel NS5B resistance-associated substitution (RAS), L204F, representing 1.5% of the viral population at baseline, enriched to 71% and 91.6% during and after treatment failure, respectively. UDPS of NS5B from Pt2 indicated a mixed infection of approximately 1:5, GT1a:GT4d, at baseline and GT4d during failure. Phylogenetic analysis of NS5A sequences indicated no clustering of HCV strains from patients achieving SVR vs patients who relapsed. The mean genetic distance in NS5A sequences was 5.8%, while a lower genetic distance (3.1%) was observed in NS5B sequences. Conclusion:Results from these analyses confirm the importance of UDPS in the analysis of viral quasispecies variability and the identification of novel RASs potentially associated with DAA treatment failure in HCV GT4-infected patients.

Dataset Information

Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy.

Publications

Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy.

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