Prolonged infection with HIV leads to loss of CD4 T cells and gradual deterioration of immune control. Viral diversity, host genetics as well as cellular and humeral immunity have all been considered important factors in determining the rate of HIV disease progression. The association of specific HLA class I alleles with the rate of HIV disease progression and the evidence for genetic imprinting of immune pressure by cytotoxic T lymphocytes (CTL) on the viral genome, support an especially crucial role of HIV specific CTL responses in maintaining relative control of in vivo HIV replication. Studies in SIV infected monkeys and HIV infected humans analyzed during early viral infection further suggest that responses induced in the first few weeks of infection may exert significant immune control, thereby limiting the initial, damaging hit on the immune system, especially the CD4 T cell. However, despite some existing work in cohorts of acutely infected individuals, our knowledge on the events surrounding acute infection, the first wave of cellular immune response and the effect viral diversity in the incoming virus may have on the long-term outcome of the infection, remain largely unknown. As these factors may set the stage for the rate of HIV disease progression, their detailed understanding and assessing their interdependence may prove especially valuable for the design of effective, prophylactic vaccine strategies. The present application aims to contribute to the advances in this field by establishing a prospective cohort of individuals identified during acute, untreated HIV infection and assess their initial viral diversity and evolving cellular immune response in relation to viral set point. Specifically, the proposed studies aim to address the questions as to whether the extend of viral diversity in the earliest detectable virus determines the rate of adaptation of the virus to the evolving immune response and whether infection with a more or less diverse viral inoculum is thus associated with different ability of the hosts immune system to control the virus. ? ?
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