TY - JOUR
T1 - A Randomized, Placebo-Controlled Trial Assessing the Effect of VISBIOME ES Probiotic in People with HIV on Antiretroviral Therapy
AU - A5350 and A5352s teams
AU - Presti, Rachel M.
AU - Yeh, Eunice
AU - Williams, Brett
AU - Landay, Alan
AU - Jacobson, Jeffrey M.
AU - Wilson, Cara
AU - Fichtenbaum, Carl J.
AU - Utay, Netanya
AU - Dube, Michael P.
AU - Klingman, Karin L.
AU - Estes, Jacob D.
AU - Flynn, Jacob K.
AU - Loftin, Amanda
AU - Brenchley, Jason M.
AU - Andrade, Adriana
AU - Kitch, Douglas W.
AU - Overton, Edgar T.
N1 - Publisher Copyright:
© 2021 The Author(s) 2021.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function. Methods: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample t test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test. Results: Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 μg/L; 95% CI, -48.5 to 233 μg/L) and Visbiome ES (mean change, 41.0 μg/L; 95% CI, -94.1 to 176.2 μg/L; P=.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (P>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in Gammaproteobacteria (P=.044) in the Visbiome ES arm. Conclusions: Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy-treated people with HIV.
AB - Background: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function. Methods: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample t test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test. Results: Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 μg/L; 95% CI, -48.5 to 233 μg/L) and Visbiome ES (mean change, 41.0 μg/L; 95% CI, -94.1 to 176.2 μg/L; P=.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (P>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in Gammaproteobacteria (P=.044) in the Visbiome ES arm. Conclusions: Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy-treated people with HIV.
KW - HIV
KW - Human microbiome
KW - Inflammation
KW - Probiotics
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U2 - 10.1093/ofid/ofab550
DO - 10.1093/ofid/ofab550
M3 - Article
AN - SCOPUS:85122447735
SN - 2328-8957
VL - 8
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 12
M1 - ofab550
ER -