Immunological and virological parameters determining plasma viral load trajectory and set point following HIV-1 infection. (360G-Wellcome-078927_Z_05_Z)

The pattern of HIV-1-specific CD8+ T-cell dominance may be critical for the effectiveness of these responses in controlling HIV-1 replication during primary infection. We will test this hypothesis in 36 individuals identified close to the time of infection and followed through the viral set point. Analyses for plasma viral load (pVL) trajectory will be performed with individuals stratified according to HLA class I alleles previously associated with slow disease progression. ELISpot assays will be performed to measure HIV-1-specific CD8+ T-cell responses and map epitopes longitudinally. Responses will be phenotyped using multi-parametric flowcytometry and phenotype related to function (cytokine, granzyme and perforin production, degranulation, proliferation) and pVL trajectory. HIV-1 RNA will be sequenced at intervals to assess viral escape, association with patterns of epitope recognition and impact on magnitude of responses. Understanding how HLA class I polymorphisms and escape mutations influence the patterns of HIV-1-specific CD8+ T-cell dominance and identifying the functional phenotypes of CD8+ T-cells critical for the control of HIV-1 replication will contribute to the design of vaccines that elicit effective CD8+ T-cell responses to control HIV-1 replication following infection and result in low set points. The latterare associated with slow progression and reduced risk of HIV-1 transmission.