Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression

Autor: Sharon Walmsley, Michael F. Saikali, Carolyn L. Cummins, Rupert Kaul, Rodney Rousseau, Colin Kovacs, Rabea Nadeem, Fat Malazogu, Leah Szadkowski, Sanja Huibner
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
Male
RNA viruses
0301 basic medicine
Physiology
HIV Infections
Disease
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Pathology and Laboratory Medicine
Biochemistry
White Blood Cells
0302 clinical medicine
Immunodeficiency Viruses
Animal Cells
Medicine and Health Sciences
Public and Occupational Health
Treatment Failure
030212 general & internal medicine
Multidisciplinary
medicine.diagnostic_test
T Cells
Middle Aged
Vaccination and Immunization
Body Fluids
Vaccination
Phenotype
Blood
Anti-Retroviral Agents
Medical Microbiology
Viral Pathogens
Viruses
Medicine
Female
Tumor necrosis factor alpha
Cellular Types
Pathogens
Anatomy
Research Article
Adult
Immune Cells
Science
Immunology
CD4-CD8 Ratio
Vascular Cell Adhesion Molecule-1
Antiretroviral Therapy
Cytotoxic T cells
Context (language use)
Microbiology
Blood Plasma
Flow cytometry
Immune Activation
03 medical and health sciences
Antiviral Therapy
Retroviruses
medicine
Humans
Microbial Pathogens
Blood Cells
Surrogate endpoint
business.industry
Homing (biology)
Lentivirus
Organisms
Immunity
Biology and Life Sciences
HIV
HLA-DR Antigens
Cell Biology
CD4 Lymphocyte Count
Blood Counts
Cross-Sectional Studies
030104 developmental biology
Leukocytes
Mononuclear
Linear Models
Preventive Medicine
business
Biomarkers
CD8
Zdroj: PLoS ONE, Vol 16, Iss 7, p e0254149 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: ObjectiveSerious 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.MethodsBlinded 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.ResultsINR participants demonstrated a reduced CD4/CD8 ratio (pConclusionsPeripheral 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.
Databáze: OpenAIRE
Externí odkaz: