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Circulating (1→3)-β-D-Glucan is associated with immune activation during HIV infection

Montreal Primary HIV-infection Study and Canadian HIV and Aging Cohort Study Groups, Mehraj, V., Ramendra, R., Isnard, S., Dupuy, F. P., Ponte, R., Chen, J., Kema, I., Jenabian, M-A., Costiniuk, C., Lebouché, B., Thomas, R., Coté, P., Leblanc, R., Baril, J-G., Durand, M., Chartrand-Lefebvre, C., Tremblay, C., Ancuta, P., Bernard, N. F., Sheppard, D. C. & Routy, J-P., 15-Jan-2020, In : Clinical Infectious Diseases. 70, 2, p. 232-241 10 p.

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  • Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection

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DOI

  • Montreal Primary HIV-infection Study and Canadian HIV and Aging Cohort Study Groups
  • Vikram Mehraj
  • Rayoun Ramendra
  • Stephane Isnard
  • Franck P Dupuy
  • Rosalie Ponte
  • Jun Chen
  • Ido Kema
  • Mohammad-Ali Jenabian
  • Cecilia Costiniuk
  • Bertrand Lebouché
  • Réjean Thomas
  • Pierre Coté
  • Roger Leblanc
  • Jean-Guy Baril
  • Madeleine Durand
  • Carl Chartrand-Lefebvre
  • Cécile Tremblay
  • Petronela Ancuta
  • Nicole F Bernard
  • Donald C Sheppard
  • Jean-Pierre Routy

BACKGROUND: Microbial translocation from the gut to circulation contributes to immune activation during HIV infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Gut fungal colonization increases during HIV infection and elevated systemic levels of the fungal polysaccharide (13)--D-Glucan (DG) have been reported in people living with HIV (PLWH). We assessed plasma DG in 146 early and chronic PLWH and investigated its contribution to systemic immune activation.

METHODS: Cross-sectional and longitudinal assessment of plasma DG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, pro-inflammatory cytokines, and DG-specific receptor expression on monocytes and NK cells.

RESULTS: Plasma DG levels were elevated during early and chronic HIV infection and persisted despite long-term ART. DG increased over 24-months without ART (p=0.01) but remained unchanged after 24-months of treatment (p>0.99). DG correlated negatively with CD4 T-cell count (r=-0.252; p<0.001), and positively with time to ART initiation (r=0.254; p=0.04), viral load (r=0.350; p=0.002), I-FABP (r=0.384; p=0.001), LPS (r=0.267; p<0.001), and sCD14 (r=0.388; p=0.001). Elevated DG correlated positively with IDO-1 enzyme activity (r=0.345; p=0.004), Tregs frequency (r=0.410; p=0.006), activated CD38+HLA-DR+ CD4 (r=0.652; p<0.001) and CD8 T-cells (r=0.687; p<0.001), and negatively with Dectin-1 (r=-0.474; p=0.01) and NKp30 (r=-0.614; p=0.009) expression on monocytes and NK cells, respectively.

CONCLUSION: PLWH have elevated plasma DG in correlation with markers of disease progression, gut damage, bacterial translocation and inflammation. Early ART initiation prevents further DG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non-AIDS events.

Original languageEnglish
Pages (from-to)232-241
Number of pages10
JournalClinical Infectious Diseases
Volume70
Issue number2
Early online date16-Mar-2019
Publication statusPublished - 15-Jan-2020

ID: 78467035