Quasispecies dynamics and treatment outcome during early hepatitis C infection in a cohort of HIV-infected men

Abdelrahman, Tamer (2015) Quasispecies dynamics and treatment outcome during early hepatitis C infection in a cohort of HIV-infected men. PhD thesis, University of Glasgow.

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Abstract

Hepatitis C virus (HCV) is emerging as one of the leading causes of morbidity and mortality in individuals infected with HIV and has overtaken AIDS-defining illnesses as a cause of death in HIV patient populations who have access to highly active antiretroviral therapy. For many years, the clonal analysis was the reference method for investigating viral diversity. In this thesis, a next generation sequencing (NGS) approach was developed using 454 pyrosequencing and Illumina-based technology. A sequencing pipeline was developed using two different NGS approaches, nested PCR, and metagenomics. The pipeline was used to study the viral populations in the sera of HCV-infected patients from a unique cohort of 160 HIV-positive patients with early HCV infection. These pipelines resulted in an improved understanding of HCV quasispecies dynamics, especially regarding studying response to treatment. Low viral diversity at baseline correlated with sustained virological response (SVR) while high viral diversity at baseline was associated with treatment failure. The emergence of new viral strains following treatment failure was most commonly associated with emerging dominance of pre-existing minority variants rather than re-infection. In the new era of direct-acting antivirals, next generation sequencing technologies are the most promising tool for identifying minority variants present in the HCV quasispecies populations at baseline. In this cohort, several mutations conferring resistance were detected in genotype 1a treatment-naïve patients. Further research into the impact of baseline HCV variants on SVR rates should be carried out in this population. A clearer understanding of the properties of viral quasispecies would enable clinicians to make improved treatment choices for their patients.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Hepatitis C, antiviral resistance, treatment, viral diversity.
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > R Medicine (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Funder's Name: Medical Research Council (MRC)
Supervisor's Name: John, Dr McLauchlan and Emma, Dr Thomson
Date of Award: 2015
Depositing User: Dr T Abdelrahman
Unique ID: glathesis:2015-7402
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 07 Jun 2016 08:43
Last Modified: 23 Jun 2017 10:12
URI: http://theses.gla.ac.uk/id/eprint/7402

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