Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era
Background Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibi...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/108669 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/108669 |
| Access Level: | acceso abierto |
| Palabra clave: | 578.7 616.98 LLV HIV-1 Activation Senescence Infammation Ciencias Biomédicas Enfermedades infecciosas 2420 Virología 3205.05 Enfermedades Infecciosas |
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Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI eraLara Aguilar, VioletaLlamas Adán, ManuelBrochado Kith, ÓscarCrespo Bermejo, CeliaGrande García, SergioArca Lafuente, SoniaDe los Santos, IgnacioPrado, CarmenAlía, MarioSainz Pinós, CoralFernández Rodríguez, AmandaMartín Carbonero, LuzMadrid González, RicardoBriz, Verónica578.7616.98LLVHIV-1ActivationSenescenceInfammationCiencias BiomédicasEnfermedades infecciosas2420 Virología3205.05 Enfermedades InfecciosasBackground Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC). Methods Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.</jats:p> Results The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups. Conclusion LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.Springer NatureUniversidad Complutense de Madrid20242024-08-1920242024-08-19journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/108669reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengCIII Not available PI18CIII%2F00020CIBERINFECC Not available CB21%2F13%2F00044CIBERINFECC Not available CB21%2F13%2F00107open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1086692026-06-02T12:44:21Z |
| dc.title.none.fl_str_mv |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| title |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| spellingShingle |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era Lara Aguilar, Violeta 578.7 616.98 LLV HIV-1 Activation Senescence Infammation Ciencias Biomédicas Enfermedades infecciosas 2420 Virología 3205.05 Enfermedades Infecciosas |
| title_short |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| title_full |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| title_fullStr |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| title_full_unstemmed |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| title_sort |
Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era |
| dc.creator.none.fl_str_mv |
Lara Aguilar, Violeta Llamas Adán, Manuel Brochado Kith, Óscar Crespo Bermejo, Celia Grande García, Sergio Arca Lafuente, Sonia De los Santos, Ignacio Prado, Carmen Alía, Mario Sainz Pinós, Coral Fernández Rodríguez, Amanda Martín Carbonero, Luz Madrid González, Ricardo Briz, Verónica |
| author |
Lara Aguilar, Violeta |
| author_facet |
Lara Aguilar, Violeta Llamas Adán, Manuel Brochado Kith, Óscar Crespo Bermejo, Celia Grande García, Sergio Arca Lafuente, Sonia De los Santos, Ignacio Prado, Carmen Alía, Mario Sainz Pinós, Coral Fernández Rodríguez, Amanda Martín Carbonero, Luz Madrid González, Ricardo Briz, Verónica |
| author_role |
author |
| author2 |
Llamas Adán, Manuel Brochado Kith, Óscar Crespo Bermejo, Celia Grande García, Sergio Arca Lafuente, Sonia De los Santos, Ignacio Prado, Carmen Alía, Mario Sainz Pinós, Coral Fernández Rodríguez, Amanda Martín Carbonero, Luz Madrid González, Ricardo Briz, Verónica |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad Complutense de Madrid |
| dc.subject.none.fl_str_mv |
578.7 616.98 LLV HIV-1 Activation Senescence Infammation Ciencias Biomédicas Enfermedades infecciosas 2420 Virología 3205.05 Enfermedades Infecciosas |
| topic |
578.7 616.98 LLV HIV-1 Activation Senescence Infammation Ciencias Biomédicas Enfermedades infecciosas 2420 Virología 3205.05 Enfermedades Infecciosas |
| description |
Background Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC). Methods Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.</jats:p> Results The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups. Conclusion LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-08-19 2024 2024-08-19 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.14352/108669 |
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https://hdl.handle.net/20.500.14352/108669 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
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CIII Not available PI18CIII%2F00020 CIBERINFECC Not available CB21%2F13%2F00044 CIBERINFECC Not available CB21%2F13%2F00107 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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Springer Nature |
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Springer Nature |
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reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
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Universidad Complutense de Madrid (UCM) |
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Docta Complutense |
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