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Acute HCV in HIV positive men; viral evolution and cellular immune responses

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Title: Acute HCV in HIV positive men; viral evolution and cellular immune responses
Authors: Thomson, Emma Cassandra
Item Type: Thesis or dissertation
Abstract: Background: The natural history of early HCV infection has been only partially characterised previously, as primary infection is usually asymptomatic. An emerging epidemic of acute HCV virus (HCV) infection in HIV-positive men in Europe, Australia and the USA has allowed the recruitment of new cohorts of patients with early HCV. We aimed to describe the natural history of virus evolution and cellular immune responses in a rare cohort of acute HCV infected HIV-positive patients in order to identify key determinants of spontaneous clearance. Methods: 110 patients were recruited and followed at 1-3 monthly intervals for a median period of 3 years. HCV E2 envelope, NS5B polymerase and NS5A genes were amplified at multiple time points using PCR and cloning techniques from plasma, liver and lymphocytes. A library of 2295 HCV E2 sequences were available for analysis .The functional immune response was assessed by ELISpot and flow cytometry. Results: 14% of patients cleared HCV spontaneously while 86% progressed towards chronicity. Three patterns of infection were observed based on viral load dynamics; spontaneous clearance (SC) and 2 patterns of progression; plateau (PV) and fluctuating viraemia (FV). SC was associated with a >1.7log10 viral load drop within 100 days of infection (OR=2.76; p=<0.001), slow viral diversification of the envelope E2 gene and the emergence of an early multi-specific T-cell response. PV was associated with positive selection within E2 and rapid viral diversification. Superinfection with new HCV strains (40% of the cohort), delayed T-cell responses and the presence of HCV within lymphocytes were all associated with FV. CD4+ responses were particularly important in defining the final outcome of infection. Conclusions: Spontaneous clearance of acute HCV in HIV-positive men can be predicted by rapid decline in viral load, low viral diversity and T-cell response. Key words: HIV, HCV, HVR-1
Issue Date: 2011
Date Awarded: Mar-2011
URI: http://hdl.handle.net/10044/1/6812
DOI: https://doi.org/10.25560/6812
Supervisor: Main, Janice
Karayiannis, Peter
Author: Thomson, Emma Cassandra
Department: Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses

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