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Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression
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Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression
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Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression
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Journal Article
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression
2021
Overview
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. 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.sup.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. INR participants demonstrated a reduced CD4/CD8 ratio (p<0.001), 35% more CD8 activation (p = 0.02), 36% greater [alpha]4[beta]7+ 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, IFN[gamma], IL-8, IL-6, sCD14, D-Dimer, I-FABP, MCP-1, ICAM or CD8%HLA-DR+. 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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Acquired immune deficiency syndrome
/ AIDS
/ Analysis
/ Complications and side effects
/ Dimers
/ Enzyme-linked immunosorbent assay
/ Histocompatibility antigen HLA
/ HIV
/ Homing
/ Human immunodeficiency virus
/ Medicine
/ Medicine and Health Sciences
/ Monocyte chemoattractant protein 1
/ Pharmacy
/ Proteins
/ Sexually transmitted diseases
/ STD
/ T cells
