The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals.

Perkins, Molly R; Bartha, Istvan; Timmer, J Katherina; Liebner, Julia C; Wollinsky, David; Günthard, Huldrych F; Hauser, Christoph; Bernasconi, Enos; Hoffmann, Matthias; Calmy, Alexandra; Battegay, Manuel; Telenti, Amalio; Douek, Daniel C; Fellay, Jacques (2015). The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals. Journal of infectious diseases, 212(4), pp. 578-584. Oxford University Press 10.1093/infdis/jiv089

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Systemic immune activation, a major determinant of HIV disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. While human genetic variants influencing HIV viral load have been identified, it is unknown to what extent the host genetic background contributes to inter-individual differences in other determinants of HIV pathogenesis like gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty-acid binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble sCD14 (sCD14), a marker of LPS bioactivity and microbial translocation. We also assessed the correlations between HIV viral load, sCD14 and I-FABP. While we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV viral load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection.

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