Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression.
<h4>Objective</h4>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 prof...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/fed9a50b51644aa9be3d7850261b6dc1 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:fed9a50b51644aa9be3d7850261b6dc1 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:fed9a50b51644aa9be3d7850261b6dc12021-12-02T20:09:02ZActivation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression.1932-620310.1371/journal.pone.0254149https://doaj.org/article/fed9a50b51644aa9be3d7850261b6dc12021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254149https://doaj.org/toc/1932-6203<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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+.<h4>Conclusions</h4>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.Rodney K RousseauLeah SzadkowskiColin M KovacsMichael F SaikaliRabea NadeemFat MalazoguSanja HuibnerCarolyn L CumminsRupert KaulSharon L WalmsleyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254149 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Rodney K Rousseau Leah Szadkowski Colin M Kovacs Michael F Saikali Rabea Nadeem Fat Malazogu Sanja Huibner Carolyn L Cummins Rupert Kaul Sharon L Walmsley Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression. |
| description |
<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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+.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Rodney K Rousseau Leah Szadkowski Colin M Kovacs Michael F Saikali Rabea Nadeem Fat Malazogu Sanja Huibner Carolyn L Cummins Rupert Kaul Sharon L Walmsley |
| author_facet |
Rodney K Rousseau Leah Szadkowski Colin M Kovacs Michael F Saikali Rabea Nadeem Fat Malazogu Sanja Huibner Carolyn L Cummins Rupert Kaul Sharon L Walmsley |
| author_sort |
Rodney K Rousseau |
| title |
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression. |
| title_short |
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression. |
| title_full |
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression. |
| title_fullStr |
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression. |
| title_full_unstemmed |
Activation and gut-homing of peripheral T cells in HIV immunologic non-responders despite long term viral suppression. |
| title_sort |
activation and gut-homing of peripheral t cells in hiv immunologic non-responders despite long term viral suppression. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/fed9a50b51644aa9be3d7850261b6dc1 |
| work_keys_str_mv |
AT rodneykrousseau activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT leahszadkowski activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT colinmkovacs activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT michaelfsaikali activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT rabeanadeem activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT fatmalazogu activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT sanjahuibner activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT carolynlcummins activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT rupertkaul activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression AT sharonlwalmsley activationandguthomingofperipheraltcellsinhivimmunologicnonrespondersdespitelongtermviralsuppression |
| _version_ |
1718375160702042112 |