Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART

Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIVRNAandcell-associated (CA) HIVDNAandRNA.BothCA-DNAandCA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA...

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Autores: Gärtner, Kathleen, Domínguez Rodríguez, Sara, Heaney, Judith, Gkouleli, Triantafylia, Grant, Paul, Dorgham, Karim, Sauce, Delphine, Soulie, Cathia, Busby, Eloise J., Tagarro García, Alfredo, et al.
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad Europea (UEM)
Repositorio:ABACUS. Repositorio de Producción Científica
Idioma:español
OAI Identifier:oai:abacus.universidadeuropea.com:11268/16045
Acceso en línea:https://hdl.handle.net/11268/16045
Access Level:acceso abierto
Palabra clave:Enfermedades Virales de Transmisión Sexual
Terapia Antirretroviral Altamente Activa
Ciencias médicas
Inmunología
Enfermedad venérea
Goal 3: Ensure healthy lives and promote well-being for all at all ages
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spelling Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ARTGärtner, KathleenDomínguez Rodríguez, SaraHeaney, JudithGkouleli, TriantafyliaGrant, PaulDorgham, KarimSauce, DelphineSoulie, CathiaBusby, Eloise J.Tagarro García, Alfredoet al.Enfermedades Virales de Transmisión SexualTerapia Antirretroviral Altamente ActivaCiencias médicasInmunologíaEnfermedad venéreaGoal 3: Ensure healthy lives and promote well-being for all at all agesInitiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIVRNAandcell-associated (CA) HIVDNAandRNA.BothCA-DNAandCA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CARNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CARNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-a was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ Tlymphocytes were not predictive of the CA-RNA in this cross-sectional study. Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized inpaediatricclinical trialswhere the sample volumecanbe a significant limitation.20252025-07-2620242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/11268/16045reponame:ABACUS. Repositorio de Producción Científicainstname:Universidad Europea (UEM)Españolspaopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:abacus.universidadeuropea.com:11268/160452026-06-11T12:41:27Z
dc.title.none.fl_str_mv Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
title Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
spellingShingle Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
Gärtner, Kathleen
Enfermedades Virales de Transmisión Sexual
Terapia Antirretroviral Altamente Activa
Ciencias médicas
Inmunología
Enfermedad venérea
Goal 3: Ensure healthy lives and promote well-being for all at all ages
title_short Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
title_full Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
title_fullStr Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
title_full_unstemmed Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
title_sort Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
dc.creator.none.fl_str_mv Gärtner, Kathleen
Domínguez Rodríguez, Sara
Heaney, Judith
Gkouleli, Triantafylia
Grant, Paul
Dorgham, Karim
Sauce, Delphine
Soulie, Cathia
Busby, Eloise J.
Tagarro García, Alfredo
et al.
author Gärtner, Kathleen
author_facet Gärtner, Kathleen
Domínguez Rodríguez, Sara
Heaney, Judith
Gkouleli, Triantafylia
Grant, Paul
Dorgham, Karim
Sauce, Delphine
Soulie, Cathia
Busby, Eloise J.
Tagarro García, Alfredo
et al.
author_role author
author2 Domínguez Rodríguez, Sara
Heaney, Judith
Gkouleli, Triantafylia
Grant, Paul
Dorgham, Karim
Sauce, Delphine
Soulie, Cathia
Busby, Eloise J.
Tagarro García, Alfredo
et al.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Enfermedades Virales de Transmisión Sexual
Terapia Antirretroviral Altamente Activa
Ciencias médicas
Inmunología
Enfermedad venérea
Goal 3: Ensure healthy lives and promote well-being for all at all ages
topic Enfermedades Virales de Transmisión Sexual
Terapia Antirretroviral Altamente Activa
Ciencias médicas
Inmunología
Enfermedad venérea
Goal 3: Ensure healthy lives and promote well-being for all at all ages
description Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIVRNAandcell-associated (CA) HIVDNAandRNA.BothCA-DNAandCA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CARNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CARNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-a was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ Tlymphocytes were not predictive of the CA-RNA in this cross-sectional study. Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized inpaediatricclinical trialswhere the sample volumecanbe a significant limitation.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
2024
2024-01-01
2025
2025-07-26
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/11268/16045
url https://hdl.handle.net/11268/16045
dc.language.none.fl_str_mv Español
spa
language_invalid_str_mv Español
language spa
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:ABACUS. Repositorio de Producción Científica
instname:Universidad Europea (UEM)
instname_str Universidad Europea (UEM)
reponame_str ABACUS. Repositorio de Producción Científica
collection ABACUS. Repositorio de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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