Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV
IntroductionThe CD4/CD8 ratio has emerged as a useful indicator of immune dysfunction and comorbid conditions in people living with HIV (PLWH). However, its optimal cut-off value is unclear. We explored the correlation between the CD4/CD8 ratio, immunosenescence markers and comorbid conditions.Metho...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1562537/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850200355461136384 |
|---|---|
| author | Matteo Vassallo Jacques Durant Sami Addou Michel Ticchioni Roxane Fabre Roxane Fabre David Chirio Alissa Naqvi Eric Cua Leslie Ameil Maeva Godemert Christian Pradier Michel Carles |
| author_facet | Matteo Vassallo Jacques Durant Sami Addou Michel Ticchioni Roxane Fabre Roxane Fabre David Chirio Alissa Naqvi Eric Cua Leslie Ameil Maeva Godemert Christian Pradier Michel Carles |
| author_sort | Matteo Vassallo |
| collection | DOAJ |
| description | IntroductionThe CD4/CD8 ratio has emerged as a useful indicator of immune dysfunction and comorbid conditions in people living with HIV (PLWH). However, its optimal cut-off value is unclear. We explored the correlation between the CD4/CD8 ratio, immunosenescence markers and comorbid conditions.MethodsWe prospectively included PLWH on successful and stable ART (antiretroviral therapy) > 60 years old and receiving either BIC/FTC/TAF or DTG/3TC, in Nice, France. HIV-negative healthy subjects were included as controls. We measured T-cell subsets (naïve, central memory, effector memory and terminally differentiated cells) and the distribution of KLRG1 + CD57+ senescent cells. We correlated CD4/CD8 ratio, background measurements and comorbid conditions.ResultsWe included 68 PLWH (median age 69 years, 31 years on ART, median CD4/CD8 ratio 0.76). PLWH had higher levels of senescence markers than controls (n = 8). Among PLWH, adjusting for age, gender, HIV follow-up and duration on ART, those with a CD4/CD8 ratio < 0.76 had more senescent CD8+ cells (AdjOR = 0.93, 95%CI = [0.88; 0.97], p-value = 0.003). Higher levels of CD8+ senescence persisted for lower CD4/CD8 ratios, with, in addition, a significant decrease in NK cells in case of a ratio < 0.4. After adjustment, CD8+ effector memory senescent cells were significantly more abundant in PLWH with hypertension.ConclusionPLWH on successful ART display elevated immunosenescence markers, mainly on CD8+ T-cells. A CD4/CD8 cut-off value below 0.4 showed the strongest association with immune dysfunction, including NK+ cells. Such results could be useful for identifying patients requiring closer follow-up and screening for complications. |
| format | Article |
| id | doaj-art-e5bfd98b7e7a4223a51c2d6ee629ffab |
| institution | OA Journals |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-e5bfd98b7e7a4223a51c2d6ee629ffab2025-08-20T02:12:20ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-04-011210.3389/fmed.2025.15625371562537Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIVMatteo Vassallo0Jacques Durant1Sami Addou2Michel Ticchioni3Roxane Fabre4Roxane Fabre5David Chirio6Alissa Naqvi7Eric Cua8Leslie Ameil9Maeva Godemert10Christian Pradier11Michel Carles12Internal Medicine/Infectious Diseases Department, Cannes, FranceInfectious Diseases Department, University of Nice, Nice, FranceDepartment of Immunology, University of Nice, Nice, FranceDepartment of Immunology, University of Nice, Nice, FranceDepartment of Public Health, University of Nice, Nice, FrancePain Department and FHU InovPain, CHU Nice and Cote Azur University, Nice, FranceInfectious Diseases Department, University of Nice, Nice, FranceInfectious Diseases Department, University of Nice, Nice, FranceInfectious Diseases Department, University of Nice, Nice, FranceInfectious Diseases Department, University of Nice, Nice, FranceClinical Research Department, University of Nice, Nice, FranceDepartment of Public Health, University of Nice, Nice, FranceInfectious Diseases Department, University of Nice, Nice, FranceIntroductionThe CD4/CD8 ratio has emerged as a useful indicator of immune dysfunction and comorbid conditions in people living with HIV (PLWH). However, its optimal cut-off value is unclear. We explored the correlation between the CD4/CD8 ratio, immunosenescence markers and comorbid conditions.MethodsWe prospectively included PLWH on successful and stable ART (antiretroviral therapy) > 60 years old and receiving either BIC/FTC/TAF or DTG/3TC, in Nice, France. HIV-negative healthy subjects were included as controls. We measured T-cell subsets (naïve, central memory, effector memory and terminally differentiated cells) and the distribution of KLRG1 + CD57+ senescent cells. We correlated CD4/CD8 ratio, background measurements and comorbid conditions.ResultsWe included 68 PLWH (median age 69 years, 31 years on ART, median CD4/CD8 ratio 0.76). PLWH had higher levels of senescence markers than controls (n = 8). Among PLWH, adjusting for age, gender, HIV follow-up and duration on ART, those with a CD4/CD8 ratio < 0.76 had more senescent CD8+ cells (AdjOR = 0.93, 95%CI = [0.88; 0.97], p-value = 0.003). Higher levels of CD8+ senescence persisted for lower CD4/CD8 ratios, with, in addition, a significant decrease in NK cells in case of a ratio < 0.4. After adjustment, CD8+ effector memory senescent cells were significantly more abundant in PLWH with hypertension.ConclusionPLWH on successful ART display elevated immunosenescence markers, mainly on CD8+ T-cells. A CD4/CD8 cut-off value below 0.4 showed the strongest association with immune dysfunction, including NK+ cells. Such results could be useful for identifying patients requiring closer follow-up and screening for complications.https://www.frontiersin.org/articles/10.3389/fmed.2025.1562537/fullHIVCD4/CD8 ratioimmunosenescencecomorbidityimmune activation |
| spellingShingle | Matteo Vassallo Jacques Durant Sami Addou Michel Ticchioni Roxane Fabre Roxane Fabre David Chirio Alissa Naqvi Eric Cua Leslie Ameil Maeva Godemert Christian Pradier Michel Carles Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV Frontiers in Medicine HIV CD4/CD8 ratio immunosenescence comorbidity immune activation |
| title | Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV |
| title_full | Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV |
| title_fullStr | Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV |
| title_full_unstemmed | Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV |
| title_short | Immunosenescence markers in T- and NK-cells according to the CD4/CD8 ratio in successfully treated people living with HIV |
| title_sort | immunosenescence markers in t and nk cells according to the cd4 cd8 ratio in successfully treated people living with hiv |
| topic | HIV CD4/CD8 ratio immunosenescence comorbidity immune activation |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1562537/full |
| work_keys_str_mv | AT matteovassallo immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT jacquesdurant immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT samiaddou immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT michelticchioni immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT roxanefabre immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT roxanefabre immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT davidchirio immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT alissanaqvi immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT ericcua immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT leslieameil immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT maevagodemert immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT christianpradier immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv AT michelcarles immunosenescencemarkersintandnkcellsaccordingtothecd4cd8ratioinsuccessfullytreatedpeoplelivingwithhiv |