Share your thoughts on this presentation with #IAS2019 Relevance of REG3a and I-FABP on microbial translocation, inflammation and reservoir size in people living with HIV Stéphane Isnard, Rayoun Ramendra, Franck P. Dupuy, John Lin, Brandon Fombuena, Nikola Kokinov, Ido Kema, Mohammad-Ali Jenabian, Bertrand Lebouché, Cecilia T. Costiniuk, Petronela Ancuta, Nicole F. Bernard, Michael S. Silverman, Peter L. Lakatos, Madeleine Durand, Cécile Tremblay, Jean-Pierre Routy McGill university, Canada Share your thoughts on this presentation with #IAS2019

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Gut permeability vs. gut damage REG3a C-type lectin acting as an antimicrobial peptide Constitutively produced and secreted in the gut lumen by Paneth cells Translocate in the mucosa then blood only upon loss of epithelial cells-to-cell interaction Circulating levels are elevated in GVHD, Coeliac and Crohn’s disease, ulcerative colitis  Marker of gut permeability I-FABP Intracellular protein only expressed by enterocytes Found in the mucosa and blood upon enterocyte cell-death Circulating levels are elevated in enteropathies and people with chronic HIV infection.  Marker of gut epithelial damage Regenerating islet-derived protein-3α Intestinal fatty acid binding protein REG3a I-FABP I-FABP I-FABP I-FABP REG3a Major-Monfried et al. Blood 2018 Zhao et al. J Clin Invest 2018 Marafini et al. Aliment Pharmacol Ther 2014 Cheru et al. Op Forum Inf Dis 2018

Plasma REG3a levels are elevated in PLWH, including elite controllers Plasma levels of REG3a, but not I-FABP, decreased with ART.

Association between REG3a and I-FABP with different HIV and inflammation markers Parameter REG3α I-FABP Disease Progression CD4 T-cell count r=-0.28 p=0.0003 n=161 r=-0.07 p=0.4 n=160 CD8 T-cell Count r=-0.006 p=0.9 r=0.11 p=0.2 CD4/CD8 r=-0.29 p=0.0002 r=-0.35 p=0.7 Viral Load r=0.29 p=0.01 n=72 r=0.002 p=0.99 Parameter REG3α I-FABP Microbial translocation, gut inflammation LPS r=0.24 p=0.005 n=139 r=0.047 p=0.6 n=160 βDG r=0.19 p=0.03 r=0.11 p=0.2 sCD14 r=0.37 p=0.001 n=74 r=-0.0012 p=0.99 n=83 Tryptophan r=-0.41 p=0.0001 n=81 r=-0.031 p=0.8 n=87 Kynurenine r=0.30 p=0.006 p=0.12 r=0.3 n=88 Kyn/Trp r=0.39 p=0.0003 r=0.12 p=0.3 Parameter REG3α I-FABP Inflammation, immune activation IL-6 r=0.53 p<0.0001 n=139 r=0.11 p=0.2 n=160 IL-8 r=0.51 n=190 r=0.17 p=0.04 IgG r=0.44 p=0.002 n=47 r=0.16 p=0.3 n=49 IgM r=0.2 r=-0.081 p=0.6 IgA r=-0.12 p=0.4 n=50 r=0.005 p=0.99 n=52 spearman correlations

Plasma REG3a but not I-FABP levels are associated with integrated HIV DNA in CD4 T-cells EHI ART- CHI ART- CHI ART+ EC

Thanks to all study participants Acknowledgments Poster TUPDA0103 Drs JG Baril, B Lessard, MA Charron, S Dufresne, ME Turgeon, S Vézina, E Huchet, JP Kerba, M Poliquin, S Poulin, P Rochette, P Junod, D Longpré, R Pilarski, E Sasseville, L Charest, A Hamel, A Cloutier-Blais, S Massoud, F Chano, B Trottier McGill University Health Centre Dr Jean-Pierre Routy Rayoun Ramendra Dr Franck P Dupuy Dr Vikram Mehraj John Lin Josée Girouard Angie Massicotte Brandon Fombuena CVIS Drs C Costiniuk, B Lebouché, A de Pokomandy, J Szabo, J Cox, LP Haraoui, M Klein Dr P Ancuta Dr N Chomont Dr C Tremblay Dr M Durand, Dr C Chartrand-Lefebvre Rejean Thomas Dr R Leblanc Montreal Primary HIV-infection cohort Canadian HIV infected Slow Progressors Canadian HIV and Aging Cohort Scholarship Thanks to all study participants 7