Complex patterns of HCV infection are increasingly reported, particularly in highly exposed individuals, with multiple and variable subtype profiles seen in many chronic patients. This study aims to address some of the questions arising from this increasingly diverse and dynamic picture, both within hosts and at a population level. In Chapter 2 I find evidence for a highly dynamic infection profile in acute HCV, both in terms of viral load and the dominant subtype. I extrapolate these observations from individual patients to formulate a model of HCV transmission across a high-risk population in order to predict the impact of current and anticipated interventions in Chapters 3 and 4. I show that antiviral therapy and a putative vaccination can still have a significant impact on HCV prevalence at the population level, even when the latter offers only partial protection and in the epidemiological background of ongoing exposure. Thus, in an epidemic with more than one circulating strain it will be crucial for any individual or combination of interventions to target all variants present. In Chapter 5 I demonstrate that early viral load kinetics of patients initiating treatment are indicative of treatment outcome. Strain differences are also evident in the virologic response to treatment with hard-to-treat genotype 1 exhibiting a slower rate of viral load decline than genotypes 2 and 3.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:559853 |
| Date | January 2011 |
| Creators | Smith, Jennifer |
| Contributors | McLean, Angela ; Klenerman, Paul |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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