1. Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression.
- Author
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Rousseau RK, Szadkowski L, Kovacs CM, Saikali MF, Nadeem R, Malazogu F, Huibner S, Cummins CL, Kaul R, and Walmsley SL
- Subjects
- Adult, Anti-Retroviral Agents therapeutic use, CD4 Lymphocyte Count, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes metabolism, Cross-Sectional Studies, Female, HIV Infections drug therapy, HLA-DR Antigens metabolism, Humans, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear metabolism, Linear Models, Lymphocyte Activation, Male, Middle Aged, Phenotype, Treatment Failure, Vascular Cell Adhesion Molecule-1 blood, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology
- Abstract
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/mm3; 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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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