Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers

Elite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 1...

ver descrição completa

Detalhes bibliográficos
Autores: Rosás-Umbert, Miriam, Llano, Anuska, Bellido, Rocío, Olvera, Alex, Ruiz-Riol, Marta, Rocafort, Muntsa, Fernández, Marco A, Cobarsi, Patricia, Crespo, Manel, Dorrell, Lucy, Del Romero, Jorge, Alcamí, José, Paredes, Roger, Brander, Christian, Mothe, Beatriz
Tipo de documento: artigo
Data de publicação:2019
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/13060
Acesso em linha:http://hdl.handle.net/20.500.12105/13060
Access Level:Acceso aberto
Palavra-chave:Adult
Anti-Retroviral Agents
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cohort Studies
Female
HIV Infections
HIV-1
Humans
Lymphocyte Activation
Male
Middle Aged
Viral Load
Viral Tropism
Viremia
Virus Replication
id ES_eee08e90ac3eef9c99ede5d540c32c90
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/13060
network_acronym_str ES
network_name_str España
repository_id_str
spelling Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllersRosás-Umbert, MiriamLlano, AnuskaBellido, RocíoOlvera, AlexRuiz-Riol, MartaRocafort, MuntsaFernández, Marco ACobarsi, PatriciaCrespo, ManelDorrell, LucyDel Romero, JorgeAlcamí, JoséParedes, RogerBrander, ChristianMothe, BeatrizAdultAnti-Retroviral AgentsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCohort StudiesFemaleHIV InfectionsHIV-1HumansLymphocyte ActivationMaleMiddle AgedViral LoadViral TropismViremiaVirus ReplicationElite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control. The in-depth analysis of these subjects involved the study of cell tropism of circulating virus, evidence for HIV superinfection, cellular immune responses to HIV, as well as an examination of viral adaptation to host immunity by Gag sequencing. Our data demonstrate that a poor capacity of T cells to mediate in vitro viral suppression, even in the context of protective HLA alleles, predicts a loss of viral control. In addition, the data suggest that inefficient viral control may be explained by an increase of CD8 T-cell activation and exhaustion before LoC. Furthermore, we detected a switch from C5- to X4-tropic viruses in 4 individuals after loss of control, suggesting that tropism shift might also contribute to disease progression in HIV controllers. The significantly reduced inhibition of in vitro viral replication and increased expression of activation and exhaustion markers preceding the abrupt loss of viral control may help identify untreated HIV controllers that are at risk of losing control and may offer a useful tool for monitoring individuals during treatment interruption phases in therapeutic vaccine trials.IMPORTANCE A few individuals can control HIV infection without the need for antiretroviral treatment and are referred to as HIV controllers. We have studied HIV controllers who suddenly lose this ability and present with high in vivo viral replication and decays in their CD4+ T-cell counts to identify potential immune and virological factors that were responsible for initial virus control. We identify in vitro-determined reductions in the ability of CD8 T cells to suppress viral control and the presence of PD-1-expressing CD8+ T cells with a naive immune phenotype as potential predictors of in vivo loss of virus control. The findings could be important for the clinical management of HIV controller individuals, and it may offer an important tool to anticipate viral rebound in individuals in clinical studies that include combination antiretroviral therapy (cART) treatment interruptions and which, if not treated quickly, could pose a significant risk to the trial participants.American Society for Microbiology (ASM)Instituto de Salud Carlos IIIMinisterio de Sanidad (España)Fundación para la Innovación y la Prospectiva en Salud en EspañaUnión Europea. Comisión Europea20212021-06-0220192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/13060reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 681137open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/130602026-06-12T12:43:37Z
dc.title.none.fl_str_mv Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
title Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
spellingShingle Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
Rosás-Umbert, Miriam
Adult
Anti-Retroviral Agents
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cohort Studies
Female
HIV Infections
HIV-1
Humans
Lymphocyte Activation
Male
Middle Aged
Viral Load
Viral Tropism
Viremia
Virus Replication
title_short Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
title_full Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
title_fullStr Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
title_full_unstemmed Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
title_sort Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers
dc.creator.none.fl_str_mv Rosás-Umbert, Miriam
Llano, Anuska
Bellido, Rocío
Olvera, Alex
Ruiz-Riol, Marta
Rocafort, Muntsa
Fernández, Marco A
Cobarsi, Patricia
Crespo, Manel
Dorrell, Lucy
Del Romero, Jorge
Alcamí, José
Paredes, Roger
Brander, Christian
Mothe, Beatriz
author Rosás-Umbert, Miriam
author_facet Rosás-Umbert, Miriam
Llano, Anuska
Bellido, Rocío
Olvera, Alex
Ruiz-Riol, Marta
Rocafort, Muntsa
Fernández, Marco A
Cobarsi, Patricia
Crespo, Manel
Dorrell, Lucy
Del Romero, Jorge
Alcamí, José
Paredes, Roger
Brander, Christian
Mothe, Beatriz
author_role author
author2 Llano, Anuska
Bellido, Rocío
Olvera, Alex
Ruiz-Riol, Marta
Rocafort, Muntsa
Fernández, Marco A
Cobarsi, Patricia
Crespo, Manel
Dorrell, Lucy
Del Romero, Jorge
Alcamí, José
Paredes, Roger
Brander, Christian
Mothe, Beatriz
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Sanidad (España)
Fundación para la Innovación y la Prospectiva en Salud en España
Unión Europea. Comisión Europea
dc.subject.none.fl_str_mv Adult
Anti-Retroviral Agents
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cohort Studies
Female
HIV Infections
HIV-1
Humans
Lymphocyte Activation
Male
Middle Aged
Viral Load
Viral Tropism
Viremia
Virus Replication
topic Adult
Anti-Retroviral Agents
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cohort Studies
Female
HIV Infections
HIV-1
Humans
Lymphocyte Activation
Male
Middle Aged
Viral Load
Viral Tropism
Viremia
Virus Replication
description Elite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control. The in-depth analysis of these subjects involved the study of cell tropism of circulating virus, evidence for HIV superinfection, cellular immune responses to HIV, as well as an examination of viral adaptation to host immunity by Gag sequencing. Our data demonstrate that a poor capacity of T cells to mediate in vitro viral suppression, even in the context of protective HLA alleles, predicts a loss of viral control. In addition, the data suggest that inefficient viral control may be explained by an increase of CD8 T-cell activation and exhaustion before LoC. Furthermore, we detected a switch from C5- to X4-tropic viruses in 4 individuals after loss of control, suggesting that tropism shift might also contribute to disease progression in HIV controllers. The significantly reduced inhibition of in vitro viral replication and increased expression of activation and exhaustion markers preceding the abrupt loss of viral control may help identify untreated HIV controllers that are at risk of losing control and may offer a useful tool for monitoring individuals during treatment interruption phases in therapeutic vaccine trials.IMPORTANCE A few individuals can control HIV infection without the need for antiretroviral treatment and are referred to as HIV controllers. We have studied HIV controllers who suddenly lose this ability and present with high in vivo viral replication and decays in their CD4+ T-cell counts to identify potential immune and virological factors that were responsible for initial virus control. We identify in vitro-determined reductions in the ability of CD8 T cells to suppress viral control and the presence of PD-1-expressing CD8+ T cells with a naive immune phenotype as potential predictors of in vivo loss of virus control. The findings could be important for the clinical management of HIV controller individuals, and it may offer an important tool to anticipate viral rebound in individuals in clinical studies that include combination antiretroviral therapy (cART) treatment interruptions and which, if not treated quickly, could pose a significant risk to the trial participants.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
2019
2019-01-01
2021
2021-06-02
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 http://hdl.handle.net/20.500.12105/13060
url http://hdl.handle.net/20.500.12105/13060
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 681137
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://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
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology (ASM)
publisher.none.fl_str_mv American Society for Microbiology (ASM)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423786279829504
score 15.812429

Registros relacionados