Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Disentangling human tolerance and resistance against HIV
Roland R. Regoes, Paul J. Mclaren, Manuel Battegay, Enos Bernasconi, Alexandra Calmy, Huldrych F. Günthard, Matthias Hoffmann, Andri Rauch, Amalio Telenti, Jacques Fellay

Last modified: 2014-06-09



In evolutionary ecology, "tolerance" is defined as an evolutionary response of a host population against pathogen pressure, which is characterized by the lack of pathogenesis despite high pathogen loads. To-date tolerance has not been quantified and disentangled from host resistance in any clinically relevant infection of humans. Using data from the Swiss HIV Cohort Study, we studied if there is variation in tolerance to HIV in humans.  We found that tolerance differs significantly across Human Leukocyte Antigen B (HLA-B) genotypes, while classical protective HLA-B alleles are associated with resistance but not with tolerance. Furthermore, we found increased tolerance against HIV in HLA-B heterozygotes and young individuals.  Thus, tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to new treatment approaches.