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Population Dynamics of Human Immunodeficiency Virus


In this work, we explore the in vivo population dynamics of HIV with mathematical and computational methods. Chapter 1 examines the effects of productive unintegrated virus (uDNA) on viral dynamics in the context of free-virus and synaptic transmission. We find that productive uDNA can contribute up to 20% towards the basic reproductive ratio of HIV in vivo. If more than one unintegrated virus is required for productive infection, then uDNA does not contribute towards R0 from free virus infection. As more viruses are successfully transmitted per synapse, the lower the contribution of uDNA. Chapter 2 explores the effect of uDNA in the context of an immune response during the asymptomatic phase. We find that productive uDNA can decrease or increase set-point viral levels compared to the case of inert uDNA, and this depends on the rate of viral production and the strength of the immune response. In Chapter 3, we explore a two-compartment model to explain the observed difference in the multiplicity of infection of HIV between the lymphoid system and the blood. Our model suggests that the absence of strong synaptic transmission in the peripheral blood tends to create many singly infected cells - reducing the proportion of multiply infected cells. Although this simple mechanism can explain much of the difference between the two systems, we also conclude that there must be some additional mechanism that is reducing the number of highly multiply infected cells in the blood.

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