This thesis is concerned with exploring how cell heterogeneity and drug resistance can cause long term persistence of HIV. We examine models of multiple viral strains to assess the impact of drug resistance on viral persistence and extend our cell heterogeneity models to include multiple strains. Chapter 1 summarises the nature of HIV infection within host. The key barriers to HIV eradication within host and the role of mathematical models to help understand these issues are discussed. In Chapter 2 we analyse models that include cell heterogeneity. We find robust long term viral persistence is possible on therapy and differences in viral load between body compartments explained by cell heterogeneity. The inclusion of a drug sanctuary also allows low level viral load on treatment. Competition and evolutionary models of wildtype and drug resistant strains of virus are described in Chapter 3. We analyse two models containing three strains of virus with different mutation mechanisms. We find that the proportion of the minority strains of virus is determined by the number of mutations away from the dominant strain. In Chapter 4 we extend our cell heterogeneity models from Chapter 2 to include a drug resistant strain of virus. We find that when a drug sanctuary is present coexistence is possible in the absence of an evolutionary mechanism. The two compartment model also shows differential dominance whereby a different strain is dominant in each compartment. within the host. We find the latent cell reservoir acts as an archive for previously dominant viral strains when there is a mechanism for latent cell maintenance and that the balance between ongoing viral and latent cell replication determines the longevity of the archive.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:550615 |
| Date | January 2011 |
| Creators | Ward, Zoe |
| Contributors | White, Katrin |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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