De Silva, T; (2013) Molecular epidemiology of Human Immunodeficiency Viruses and exploration of host immune responses associated with long-term control of HIV-2 infection in West Africa. Doctoral thesis , UCL (University College London).

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Abstract

Unlike many parts of the world, both HIV-1 and HIV-2 are endemic in West Africa. The work in this thesis was based on a clinic cohort at the Medical Research Council Laboratories in the Gambia and a community cohort based in Caió, a rural village in Guinea-Bissau. Although HIV-2 was the dominant infection in these countries two decades ago, HIV-1 has increased rapidly in recent years. Chapter 3 demonstrates that although HIV-1 CRF02_AG is responsible for most HIV-1 infections in both cohorts, the subtype distribution varies considerably – including the presence of a novel circulating recombinant form (CRF49_cpx) in the Gambia, accounting for approximately 15% of all cases. Chapter 4 applies modern phylogenetic and phylodynamic techniques to viral sequences from rural Guinea-Bissau to characterise the molecular epidemiology and population dynamics of HIV-1 and HIV-2 in this region. Viruses from HIV-2 elite controllers and progressors can share a most recent common ancestor, suggesting that host factors are responsible for the dichotomous outcomes observed in HIV-2 infection. Chapter 5 explores whether humoral immunity plays a role in HIV-2 non-progression. Neutralising antibody responses of remarkable magnitude and breadth are seen in the plasma of HIV-2 infected subjects, yet there is no direct relationship to viral control. Chapter 6 demonstrates that polyfunctional HIV-2 Gag-specific CD8+ T-cell responses are, however, associated with control of HIV-2. The phenotype of these CD8+ T-cells varies from what is thought to be important in HIV-1 control. In contrast to HIV-1, escape from both humoral and cellular immune responses may be limited in HIV-2. The aim of this work was to help understand the spread and transmission of HIV-1 and HIV-2 in West Africa, as well as to provide insight into why most HIV-2 infected individuals behave as long term non-progressors, whereas others progress to AIDS like their HIV-1 infected counterparts.

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