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Title: An investigation into the genetic variation of hepatitis C virus in patients coinfected with HIV
Author: King, S.
ISNI:       0000 0004 6058 4992
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2015
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Co-infection with HIV in patients with chronic HCV infection is a common occurrence, which accelerates disease progression and the rate of liver fibrosis. Current literature report conflicting results on the effect of HIV co-infection on HCV at the genetic level. This thesis sets out to further explore the genetic variation of HCV in this group of patients, and use new techniques which may impact upon the diagnosis and management of HCV. In resource-limited settings such as sub-Saharan Africa, there is a paucity of data concerning rates of active HCV infection in patients with HIV infection. The limited infrastructure and financial restrictions are contributing factors in this. Consequently, cheaper and novel diagnostic procedures are required to promote testing in these important cohorts. A real-time PCR assay for use with pooled plasma and dried plasma spot specimens was developed to screen a large cohort of HIV-infected individuals from Ghana and assess its suitability for screening in such a setting. The prevalence of active HCV infection in this cohort was similar to previous estimates from blood donors but was much lower than estimates from serological tests, highlighting the potential risks in relying on these tests alone in this region. The diversity of strains found within this population agreed well with previous studies. As the yield of HCV infections was low in Ghana, further studies were completed with the UK and European cohort. A deep sequencing approach was utilised to two effects. The first focussed on a specific notable polymorphism – Q80K in the NS3 gene – to determine whether deep sequencing would benefit the clinic in the detection of this polymorphism at low frequencies, which are below the threshold of detection by traditional population sequencing. The second use of deep sequencing aimed to determine the impact of HIV co-infection on the presence of resistance associated mutations occurring at baseline, studying the largest cohort to date. The Q80K polymorphism was not observed in any sample as a minority variant, suggesting that the current clinical procedures for pre-treatment screening are suitable and provide sufficient sensitivity. Overall, resistance mutations were relatively common among patients and it was observed that, generally, there were no differences in the prevalences of resistance mutations between HCV mono-infected and HIV/HCV co-infected patients. This finding is in agreement with previous small-scale studies. This work has direct clinical implications on the use of deep sequencing for screening patients for the presence of resistance mutations. Furthermore, it suggests that co-infected individuals are not at risk of further complications for the treatment of HCV.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral