Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase

Detalhes bibliográficos
Autor(a) principal: Passos, Daniela Ferreira
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/22069
Resumo: Human immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression.
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spelling 2021-08-25T22:55:56Z2021-08-25T22:55:56Z2021-03-31http://repositorio.ufsm.br/handle/1/22069Human immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression.A replicação descontrolada do vírus da imunodeficiência humana (HIV) resulta na Síndrome da Imunodeficiência Adquirida (AIDS). A terapia antirretroviral (TARV) reduz a morbidade e a mortalidade, mas a inflamação e ativação imune permanecem. Nessa tese, dois parâmetros são avaliados em indivíduos HIV positivos sob TARV em supressão viral: a razão CD4/CD8 e a atividade da adenosina desaminase (ADA). CD4/CD8 e sua relação com comorbidades e envelhecimento foi avaliada em um estudo retrospectivo com 352 indivíduos HIV positivos sob TARV. Apesar da alta prevalência de CD4/CD8 <1 (68%) e de comorbidades (62%), não foi observada associação entre elas. A prevalência de comorbidades aumentou com o envelhecimento, enquanto a diminuição de CD4/CD8 se mostrou associada somente a doenças neurocognitivas. A investigação da ADA foi feita através da análise da atividade da ADA no soro e da ecto-ADA em células mononucleares do sangue periférico (PBMCs) de 47 indivíduos HIV positivos e 71 controles, bem como parâmetros séricos de estresse oxidativo. O grupo HIV mostrou um aumento da atividade da ADA no soro e dos níveis de espécies reativas do oxigênio (EROS), e redução da atividade da E-ADA em PBMCs. O aumento da atividade da ADA no soro no grupo HIV se mostrou associado à CD4/CD8<1 (66%) e níveis elevados de EROS, enquanto a diminuição da E-ADA nas PBMCs acompanhou a queda na razão CD4/CD8. Uma prevalência alta de CD4/CD8<1 foi observada nos dois estudos, e a atividades da ADA se mostraram associadas à razão CD4/CD8. Os dois marcadores estudados demonstram a permanência da disfunção imune nos indivíduos HIV positivos em TARV, independentemente da duração do tratamento e do tempo de supressão viral nos indivíduos HIV positivos sob TARV.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessHIV (Vírus da Imunodeficiência Humana)TARVCD4/CD8Adenosina desaminaseAdenosine deaminaseCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICADisfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminaseImmune dysfunction in hiv-positive individuals under antiretroviral therapy: role of CD4/CD8 ratio and the activity of the enzyme adenosine deaminaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisLeal, Daniela Bitencourt Rosahttp://lattes.cnpq.br/3639683273462361Schetinger, Maria Rosa ChitolinaMartínez, Ana Maria Barral deSpanevello, Roselia MariaBarbosa, Nilda Berenice de VargasCruz, Ivana Beatrice Mânica dahttp://lattes.cnpq.br/9110708054091270Passos, Daniela Ferreira200800000002600600600600600600600600ebd6d0bc-4e14-43fd-8d4e-ad9ebe640af2a886ca2c-ea46-4e57-aa6e-57dfe677f3b9e31536a8-f5a8-4f54-b813-f9fc8b2e2686d708b1f4-60fc-4791-81b3-e0f8583e10f8da7d65ae-3939-4ddc-8509-095f119250520198eecb-263d-4159-82c5-3698b0253f4f55d5df61-bdaf-4677-bad9-6430c03f8250reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2021_PASSOS_DANIELA.pdfTES_PPGCBBT_2021_PASSOS_DANIELA.pdfTeseapplication/pdf10272350http://repositorio.ufsm.br/bitstream/1/22069/1/TES_PPGCBBT_2021_PASSOS_DANIELA.pdf63ae18b97d61f1aa856e10ef86305cd8MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
dc.title.alternative.eng.fl_str_mv Immune dysfunction in hiv-positive individuals under antiretroviral therapy: role of CD4/CD8 ratio and the activity of the enzyme adenosine deaminase
title Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
spellingShingle Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
Passos, Daniela Ferreira
HIV (Vírus da Imunodeficiência Humana)
TARV
CD4/CD8
Adenosina desaminase
Adenosine deaminase
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
title_full Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
title_fullStr Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
title_full_unstemmed Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
title_sort Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
author Passos, Daniela Ferreira
author_facet Passos, Daniela Ferreira
author_role author
dc.contributor.advisor1.fl_str_mv Leal, Daniela Bitencourt Rosa
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3639683273462361
dc.contributor.advisor-co1.fl_str_mv Schetinger, Maria Rosa Chitolina
dc.contributor.referee1.fl_str_mv Martínez, Ana Maria Barral de
dc.contributor.referee2.fl_str_mv Spanevello, Roselia Maria
dc.contributor.referee3.fl_str_mv Barbosa, Nilda Berenice de Vargas
dc.contributor.referee4.fl_str_mv Cruz, Ivana Beatrice Mânica da
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/9110708054091270
dc.contributor.author.fl_str_mv Passos, Daniela Ferreira
contributor_str_mv Leal, Daniela Bitencourt Rosa
Schetinger, Maria Rosa Chitolina
Martínez, Ana Maria Barral de
Spanevello, Roselia Maria
Barbosa, Nilda Berenice de Vargas
Cruz, Ivana Beatrice Mânica da
dc.subject.por.fl_str_mv HIV (Vírus da Imunodeficiência Humana)
TARV
CD4/CD8
Adenosina desaminase
topic HIV (Vírus da Imunodeficiência Humana)
TARV
CD4/CD8
Adenosina desaminase
Adenosine deaminase
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv Adenosine deaminase
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Human immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-08-25T22:55:56Z
dc.date.available.fl_str_mv 2021-08-25T22:55:56Z
dc.date.issued.fl_str_mv 2021-03-31
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dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
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dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Bioquímica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
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