Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression Article Swipe
Rodney Rousseau
,
Leah Szadkowski
,
Colin Kovacs
,
Michael F. Saikali
,
Rabea Nadeem
,
Fat Malazogu
,
Sanja Huibner
,
Carolyn L. Cummins
,
Rupert Kaul
,
Sharon Walmsley
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0254149
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0254149
Objective Serious non-AIDS disease events (SNAE) are experienced disproportionately by immunologic non-responders (INRs), HIV-infected individuals who do not restore CD4 T cells in blood despite effective viral suppression. We aimed to characterize the inflammatory biomarker profile of the INR phenotype. Methods Blinded cross-sectional cohort study comparing markers of immune activation and gut homing between INR and non-INR individuals. HIV-positive participants had HIV RNA suppression on antiretroviral therapy and were categorized as either INR (N = 36) or Clinical Responders (“CR”; CD4>350/mm 3 ; N = 47). 18 HIV-negative comparator individuals were included. Cellular markers were assessed by flow cytometry, with soluble markers assessed by ELISA and LC/MS-MS. Multivariable linear regression models estimated the association between INR phenotype and markers, adjusting for age, sex, duration of ART, and recent infection/vaccination. Results INR participants demonstrated a reduced CD4/CD8 ratio (p<0.001), 35% more CD8 activation (p = 0.02), 36% greater α4β7+ CD4 T cells (p<0.01), 54% more HLA-DR+ CD4 T cells (p<0.001), and 20% higher plasma VCAM (p<0.01) compared to CRs. The INR phenotype was not associated with levels of Kyn/Trp, CRP, TNF, IFNγ, IL-8, IL-6, sCD14, D-Dimer, I-FABP, MCP-1, ICAM or CD8%HLA-DR+. Conclusions Peripheral CD4 non-recovery during long-term treated HIV infection is characterized by elevated CD8 activation and CD4 gut homing. Gut-focused interventions may be warranted in the INR context, and CD8 activation may serve as a surrogate endpoint for clinical interventions.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0254149
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0254149&type=printable
- OA Status
- gold
- Cited By
- 9
- References
- 20
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3183292683
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3183292683Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1371/journal.pone.0254149Digital Object Identifier
- Title
-
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppressionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-07-28Full publication date if available
- Authors
-
Rodney Rousseau, Leah Szadkowski, Colin Kovacs, Michael F. Saikali, Rabea Nadeem, Fat Malazogu, Sanja Huibner, Carolyn L. Cummins, Rupert Kaul, Sharon WalmsleyList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0254149Publisher landing page
- PDF URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0254149&type=printableDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0254149&type=printableDirect OA link when available
- Concepts
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CD8, Immunology, Medicine, Immune system, Context (archaeology), Viral load, Internal medicine, Biomarker, Cytotoxic T cell, Biology, Human immunodeficiency virus (HIV), Biochemistry, Paleontology, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 3, 2023: 1, 2022: 1, 2021: 1Per-year citation counts (last 5 years)
- References (count)
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20Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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