Impact of HLA class I alleles on immune control of adult and paediatric HIV infection. (360G-Wellcome-082369_Z_07_A)

The overarching aim of the work undertaken in the applicant's research group is to better understand what are the CD8+ T cell responses mediating effective control of adult and paediatric HIV infection. In a population-based study in KwaZulu-Natal, South Africa, we showed that only Gag-specific CD8+ T cell responses are associated with low viraemia in chronic infection. Env- or Accessory/Regulatory-specific responses are associated with high viral loads. The first aim of the proposed work is therefore to determine whether Gag-specific responses are inherently more effective than non-Gag-specific responses, or whether these discordant associations with viral load are merely the consequence of chronic infection. The second aim is to determine whether HIV adaptation at an individual level is reflected by adaptation at a population level to these effective CD8+ T cell responses in Gag. The third aim is to extend studies initiated to examine whether CD8+ T cell response play an important role in control of paediatric HIV infection. Our preliminary data suggest that they do, both via the specificity of the responses generated in infancy by the child, and also via the impact maternal CD8+ T cell responses might have on the replicative capacity of transmitted virus.