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Changes in the Fungal Marker β-D-Glucan After Antiretroviral Therapy and Association With Adiposity

Authors
  • Dirajlal-Fargo, Sahera1, 2, 3
  • Moser, Carlee4
  • Rodriguez, Katherine4
  • El-Kamari, Vanessa1, 3
  • Funderburg, Nicholas T5
  • Bowman, Emily5
  • Brown, Todd T6
  • Hunt, Peter W7
  • Currier, Judith8
  • McComsey, Grace A1, 2, 3
  • 1 University Hospitals, Cleveland Medical Center, USA , (United States)
  • 2 Rainbow Babies and Children’s Hospital, USA , (United States)
  • 3 Department of Pediatrics, Case Western Reserve University,, USA , (United States)
  • 4 Department of Biostatistics, Harvard T.H. Chan School of Public Health, USA , (United States)
  • 5 College of Medicine, School of Health and Rehabilitation Sciences,, USA , (United States)
  • 6 Department of Medicine, Johns Hopkins University, USA , (United States)
  • 7 Department of Medicine, UCSF, USA , (United States)
  • 8 Department of Medicine, UCLA, USA , (United States)
Type
Published Article
Journal
Open Forum Infectious Diseases
Publisher
Oxford University Press
Publication Date
Nov 11, 2019
Volume
6
Issue
11
Identifiers
DOI: 10.1093/ofid/ofz434
PMID: 31737737
PMCID: PMC6847395
Source
PubMed Central
Keywords
License
Unknown

Abstract

Background Bacterial translocation in HIV is associated with inflammation and metabolic complications; few data exist on the role of fungal translocation. Methods A5260s was a substudy of A5257, a prospective open label randomized trial in which treatment-naïve people with HIV (PWH) were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or raltegravir (RAL) over 96 weeks. Baseline was assessed, and changes in β-D-glucan (BDG) were assessed at weeks 4, 24, and 96. Wilcoxon rank-sum tests were used to compare distribution shifts in the changes from baseline between treatment arms and linear regression models to assess associations between BDG and measures of inflammation, body composition, and insulin resistance. Results Two hundred thirty-one participants were randomized; 90% were male, the median age was 36 years, HIV-1 RNA was 4.56 log10c/mL, and CD4 cell count was 338 cells/mm3. There was an overall increase in BDG over 96 weeks (1.57 mean fold-change; 95% confidence interval, 1.39 to 1.77) with no differences between arms. Twofold higher BDG levels at week 96 were associated with increases in trunk fat (8%) and total fat (7%) over 96 weeks ( P ≤ .035). At week 4, BDG correlated with I-FABP, a marker of enterocyte damage, and zonulin, a marker of intestinal permeability ( r = .19–.20; P < .01). Conclusions In treatment-naïve participants initiating antiretroviral therapy (ART) with TDF/FTC and either RAL or ATV/r, DRV/r, BDG, a marker of fungal translocation, increased similarly in all arms over 96 weeks. This may represent continued intestinal damage during ART and resulting fungal translocation. Higher BDG was associated with larger fat gains on ART.

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