OA11.01
Background: Early HIV host-virus interactions provide important clues to vaccine discovery and conducting acute infection studies in Africa with multiple clades is vital to development of a global vaccine.
Methods: We followed cohorts at high risk of HIV acquisition at 9 research centers in East and Southern Africa to identify volunteers with incident HIV infection. Infection date was estimated from serial antibody, p24 and/or PCR results. Volunteers were invited to bring a sexual partner for 1 visit. Follow-up was monthly for the first 3 months post-infection, quarterly through 2 years, and every 6 months thereafter. At every visit, volunteers had a symptom-directed exam including medications, and blood for viral load, CD4+ T cell counts and PBMCs.
Results: From 2006–2011, 614 seroconverters and 406 sexual partners were enrolled. Follow-up is ongoing; to date over 2,500 person years of study time has provided a valuable platform for characterizing the HIV genetic bottleneck at transmission and founder virus characteristics. T cell responses in the acute phase have been shown to be associated with virus control and viral replicative capacity with both set point viral load and CD4+ T cell decline. Disease progression varied by sub-type, with subtype-C and D-infected volunteers progressing faster than A, and HLA alleles associated with outcomes have been characterized, such as B*44, B*45, B*57 and B*81. The development and isolation of neutralizing antibodies 2–3 years post infection is being described and the level of circulating memory T follicular helper cells has been associated with the development of such antibodies. Sample panels have provided valuable to the development of pseudovirions and validating assays to detect recent infection.
Conclusions: Prospective data and samples from early infection cohorts are increasingly valuable for vaccine discovery work. Identifying host and viral factors associated with acquisition and early viral control across clades can inform the design of a global HIV vaccine.
