1. 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

2. No conflict of interest

3. 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

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

5. 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=
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

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

7. 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