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EFFECTS OF PROBIOTIC VISBIOME ES ON COLONIC MUCOSAL CD4 CELLS: RESULTS FROM A5352S
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Reported by Jules Levin
CROI 2018
webcast
http://www.croiwebcasts.org/console/player/37208?mediaType=slideVideo&&crd_fl=0&ssmsrq=1551899752076&ctms=5000&csmsrq=5056
Author(s):
Rachel Presti1, Douglas W. Kitch2, Adriana Andrade3, Alan Landay4, Jeffrey Jacobson5, Cara Wilson6, Eunice Yeh2, Jacob D. Estes7, Claire Deleage7, Karin L. Klingman8, Netanya S. Utay9, Edgar T. Overton10, Jason Brenchley8, Brett Williams4
1Washington University St Louis, St Louis, MO, USA,2Harvard University, Cambridge, MA, USA,3Johns Hopkins University, Baltimore, MD, USA,4Rush University Medical Center, Chicago, IL, USA,5Drexel College of Medicine, Philadelphia, PA, USA,6University of Cologne, Cologne, Germany,7National Cancer Institute, Frederick, MD, USA,8NIAID, Bethesda, MD, USA,9University of Texas at Galveston, Galveston, TX, USA,10University of Alabama at Birmingham, Birmingham, AL, USA
Abstract Body:
HIV infection in the GI tract results in CD4 cell depletion, especially Th17 cells, and neutrophil (PMN) infiltration, characterized by myeloperoxidase (MPO) activity. This results in impaired mucosal barrier function and systemic inflammation. ART fails to fully restore GI mucosal CD4 cells. In non-human primate models, probiotics improve GI CD4 T cell recovery during ART. In A5352s, ART-suppressed HIV-infected individuals were randomized to probiotic Visbiome ES or placebo to determine whether probiotic administration reconstitutes mucosal CD4 cells & Th17 cells and decrease PMN activity. Here, we present results from immunohistochemistry (IHC) on colonic biopsies.
At entry and after 24 weeks of intervention, participants underwent flexible sigmoidoscopy with 10 punch biopsies. Immunohistochemistry (IHC) staining was performed using antibodies to CD4, IL-17, and MPO. Stained slides were scanned using the ScanScope CS System (Aperio Technologies, Inc.); quantitative image analysis was performed to measure area of lamina propria occupied by CD4 cells, IL-17+ cells, or MPO. Changes from baseline to week 24 were calculated and arms were compared by exact Wilcoxon test.
Of 42 participants enrolled, 30 had paired biopsy specimens for analysis (15 in each arm). Mean age was 48 yrs (range 25,64); 27 males; median CD4 count 718 c/mm3 (range 263,1839). At baseline, the median % positive staining for CD4 in the placebo arm was 2.1 and 2.0 in the Visbiome ES arm. Median % CD4 decreased to 1.65 in the placebo arm, but only to 1.74 in the Visbiome ES arm, with a median change of -0.21 for placebo, and change of -0.03 in Visbiome (p=0.089). IL-17 staining was highly variable, but demonstrated no median change over 24 weeks (p=0.65). MPO minimally decreased in placebo from 0.18 to 0.11, with a median change of -0.04, while it increased in Visbiome from 0.14 to 0.18 for a median change of 0.05 0.18 over 24 weeks(p=0.081).
Although CD4 cells staining appeared to be more stable in the Visbiome arm when compared to placebo, similar to non-human primate studies, we failed to detect significant differences in CD4, IL-17 or MPO alterations between arms. This may be due to no effect of Visbiome, small study size, diverse nature of HIV and ART history, or short course of probiotic administration. Future analyses will assess measures of systemic inflammation and GI permeability.
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