Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás

Detalhes bibliográficos
Autor(a) principal: Pacheco, Priscila Ribeiro Guimarães
Data de Publicação: 2010
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/0013000000s3c
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/9230
Resumo: Objectives: To describe and analyze HIV-1 resistance mutational profiles associated with non- nucleoside reverse transcriptase inhibitors (NNRTIs) from patients experiencing antiretroviral therapy failure; at the main reference public Center in Goiás State. Methods: Samples from 474 patients were collected and processed according to the National Genotyping Network (RENAGENO), between 2006 and e 2009. Patient’s files (genotype exams) and medical records were used as data source. Number of TCD4 cells, HIV-1 viral load quantification, viral subtype and mutation profile assessment (TRUGENE HIV-1 Genotyping Test e ViroSeq System) were done according to the routine adopted by Central State Laboratory (LACEN). Resistance mutation profiles were identified using the Brazilian Algorithm and the Stanford Database Program. Cross resistance between NNRTIs: nevirapine, efavirenz and etravirine were analyzed. Descriptive and exploratory analyses were performed for socio-demographics variables and laboratory results (SPSS 15.0). Results: Samples from 126 adult patients were resistant to nevirapine (NVP) and efavirenz (EVF) Subtyping analysis showed a predominance of subtype B (86.1%), followed by BF1 recombinant (7.8%). Half of the patients received three or more antiretroviral therapy regimes. The most frequent mutations were 103N (72.2%) and 225H (22.2%). Mutations related to decreased etravirine (ETV) activity were detected in 8 codons: 98, 100, 101, 181, 188, 190 e 230 Intermediate ETV resistance were present in 27.0% and 15.1% of the samples, according to the Brazilian protocol and to Stanford Db Program, respectively. High-degree of ETV resistance were present in 10 samples (7.9%; IC95% 3.9-14.1), according to the Brazilian protocol Using the Stanford dB Program, 3 out of 126 patients (2.4%; IC95% 3.9-14.1) had high-degree of resistance. Clinical characteristics, number of T CD4 cells and viral load were not predictors to ETV resistance. Conclusions: The presence of at least one mutation potentially associated with decreased virological response to ETV was frequent, in a population highly exposed to NNRTIs. Otherwise high-degree of cross resistance to ETV was not common, suggesting that this drug could be helpful for patients failing to first generation NNRTIs.
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spelling Turchi, Marilia Dalvahttp://lattes.cnpq.br/3769826743537934Turchi, Marilia DalvaPereira, Gisner Alves de SouzaAraújo Filho, João Alves dehttp://lattes.cnpq.br/6210681102849208Pacheco, Priscila Ribeiro Guimarães2019-01-16T11:09:26Z2010-07-20PACHECO, Priscila Ribeiro Guimarães. Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás. 2010. 103 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2010.http://repositorio.bc.ufg.br/tede/handle/tede/9230ark:/38995/0013000000s3cObjectives: To describe and analyze HIV-1 resistance mutational profiles associated with non- nucleoside reverse transcriptase inhibitors (NNRTIs) from patients experiencing antiretroviral therapy failure; at the main reference public Center in Goiás State. Methods: Samples from 474 patients were collected and processed according to the National Genotyping Network (RENAGENO), between 2006 and e 2009. Patient’s files (genotype exams) and medical records were used as data source. Number of TCD4 cells, HIV-1 viral load quantification, viral subtype and mutation profile assessment (TRUGENE HIV-1 Genotyping Test e ViroSeq System) were done according to the routine adopted by Central State Laboratory (LACEN). Resistance mutation profiles were identified using the Brazilian Algorithm and the Stanford Database Program. Cross resistance between NNRTIs: nevirapine, efavirenz and etravirine were analyzed. Descriptive and exploratory analyses were performed for socio-demographics variables and laboratory results (SPSS 15.0). Results: Samples from 126 adult patients were resistant to nevirapine (NVP) and efavirenz (EVF) Subtyping analysis showed a predominance of subtype B (86.1%), followed by BF1 recombinant (7.8%). Half of the patients received three or more antiretroviral therapy regimes. The most frequent mutations were 103N (72.2%) and 225H (22.2%). Mutations related to decreased etravirine (ETV) activity were detected in 8 codons: 98, 100, 101, 181, 188, 190 e 230 Intermediate ETV resistance were present in 27.0% and 15.1% of the samples, according to the Brazilian protocol and to Stanford Db Program, respectively. High-degree of ETV resistance were present in 10 samples (7.9%; IC95% 3.9-14.1), according to the Brazilian protocol Using the Stanford dB Program, 3 out of 126 patients (2.4%; IC95% 3.9-14.1) had high-degree of resistance. Clinical characteristics, number of T CD4 cells and viral load were not predictors to ETV resistance. Conclusions: The presence of at least one mutation potentially associated with decreased virological response to ETV was frequent, in a population highly exposed to NNRTIs. Otherwise high-degree of cross resistance to ETV was not common, suggesting that this drug could be helpful for patients failing to first generation NNRTIs.Objetivo: descrever e analisar os padrões de mutação do HIV-1 associados com a resistência aos inibidores da transcriptase reversa não análogos dos nucleosídeos (ITRNNs), em indivíduos com falha de resposta à terapia antirretroviral (ARV), atendidos no principal serviço público HIV/aids do Estado de Goiás. Métodos: População composta por 474 pacientes submetidos à genotipagem, de acordo com os critérios da Rede Nacional de Genotipagem, no período de 2006 a 2009.Utilizou-se como fonte de dados formulários do Sistema de Controle de Exames de Genotipagem e prontuários clínicos. A contagem de células TCD4, a quantificação da carga viral e o sequenciamento viral para caracterização do subtipo e do perfil de resistência genotípica do HIV-1 (TRUGENE HIV-1 Genotyping Test e ViroSeq System) foram coletados e processados de acordo com as rotinas do Laboratório Central (LACEN). O algoritmo Brasileiro e o Banco de Dados de Stanford foram utilizados para interpretação do perfil de resistência. Foi analisada resistência cruzada entre os ITRNNs: nevirapina, efavirenz e etravirina. Foi realizada análise descritiva e exploratória para variáveis sócias demográficas, clínicas e laboratoriais (SPSS 15.0). Resultados: Foram identificados 126 pacientes adultos, com resistência à nevirapina (NVP) e ao efavirenz (EVF). O subtipo B foi predominante (86,1%), seguido pelo recombinante BF1(7,8%). Metade dos pacientes recebeu três ou mais esquemas antirretrovirais, pré-genotipagem. A mutação K103N foi a mais frequente (72,2%), seguida da P225H (22,2%). Foram detectadas mutações em oito códons, potencialmente, associadas com perda de sensibilidade à etravirina (ETV): 98, 100, 101, 106, 181, 188, 190 e 230. Padrão de resistência intermediária foi evidenciado em 27,0% e 15,1% das amostras, de acordo com algoritmo brasileiro e com Stanford, respectivamente. Dez pacientes (7,9%; IC95% 3,9-14,1) apresentaram resistência à ETV pelo algoritmo brasileiro e três (2,4%; IC95% 0,5-6,8) apresentaram alta resistência a essa droga, de acordo com Stanford. Características clínicas, número de células TCD4 e carga viral não foram preditores de resistência à ETV. Conclusão: A detecção de pelo menos uma mutação associada à perda de sensibilidade para ETV foi frequente, em população exposta aos outros ITRNNs, por tempo variado. Em contrapartida, alto grau de resistência cruzada à ETV foi pouco comum, sugerindo que essa droga possa ser útil em pacientes que não responderam aos ITRNNs de primeira linha.Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2019-01-16T10:28:25Z No. of bitstreams: 2 Dissertação - Priscila Ribeiro Guimarães Pacheco - 2010.pdf: 1413719 bytes, checksum: 77957da8696e2e80ee136f949866b0bf (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2019-01-16T11:09:26Z (GMT) No. of bitstreams: 2 Dissertação - Priscila Ribeiro Guimarães Pacheco - 2010.pdf: 1413719 bytes, checksum: 77957da8696e2e80ee136f949866b0bf (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2019-01-16T11:09:26Z (GMT). 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dc.title.eng.fl_str_mv Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
dc.title.alternative.eng.fl_str_mv Analysis of the resistance profile of human immunodeficiency virus type 1 (HIV-1) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in Goiás
title Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
spellingShingle Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
Pacheco, Priscila Ribeiro Guimarães
HIV-1
HAART
Transcriptase reversa
Inibidores da transcriptase reversa não análogos de nucleosídeos
Genotipagem
Resistência
ITRNN
HAART
Reverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Genotyping
Resistance
NNRTI
HIV-1
CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS
title_short Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
title_full Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
title_fullStr Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
title_full_unstemmed Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
title_sort Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás
author Pacheco, Priscila Ribeiro Guimarães
author_facet Pacheco, Priscila Ribeiro Guimarães
author_role author
dc.contributor.advisor1.fl_str_mv Turchi, Marilia Dalva
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3769826743537934
dc.contributor.referee1.fl_str_mv Turchi, Marilia Dalva
dc.contributor.referee2.fl_str_mv Pereira, Gisner Alves de Souza
dc.contributor.referee3.fl_str_mv Araújo Filho, João Alves de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6210681102849208
dc.contributor.author.fl_str_mv Pacheco, Priscila Ribeiro Guimarães
contributor_str_mv Turchi, Marilia Dalva
Turchi, Marilia Dalva
Pereira, Gisner Alves de Souza
Araújo Filho, João Alves de
dc.subject.por.fl_str_mv HIV-1
HAART
Transcriptase reversa
Inibidores da transcriptase reversa não análogos de nucleosídeos
Genotipagem
Resistência
ITRNN
topic HIV-1
HAART
Transcriptase reversa
Inibidores da transcriptase reversa não análogos de nucleosídeos
Genotipagem
Resistência
ITRNN
HAART
Reverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Genotyping
Resistance
NNRTI
HIV-1
CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS
dc.subject.eng.fl_str_mv HAART
Reverse transcriptase
Non-nucleoside reverse transcriptase inhibitors
Genotyping
Resistance
NNRTI
HIV-1
dc.subject.cnpq.fl_str_mv CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS
description Objectives: To describe and analyze HIV-1 resistance mutational profiles associated with non- nucleoside reverse transcriptase inhibitors (NNRTIs) from patients experiencing antiretroviral therapy failure; at the main reference public Center in Goiás State. Methods: Samples from 474 patients were collected and processed according to the National Genotyping Network (RENAGENO), between 2006 and e 2009. Patient’s files (genotype exams) and medical records were used as data source. Number of TCD4 cells, HIV-1 viral load quantification, viral subtype and mutation profile assessment (TRUGENE HIV-1 Genotyping Test e ViroSeq System) were done according to the routine adopted by Central State Laboratory (LACEN). Resistance mutation profiles were identified using the Brazilian Algorithm and the Stanford Database Program. Cross resistance between NNRTIs: nevirapine, efavirenz and etravirine were analyzed. Descriptive and exploratory analyses were performed for socio-demographics variables and laboratory results (SPSS 15.0). Results: Samples from 126 adult patients were resistant to nevirapine (NVP) and efavirenz (EVF) Subtyping analysis showed a predominance of subtype B (86.1%), followed by BF1 recombinant (7.8%). Half of the patients received three or more antiretroviral therapy regimes. The most frequent mutations were 103N (72.2%) and 225H (22.2%). Mutations related to decreased etravirine (ETV) activity were detected in 8 codons: 98, 100, 101, 181, 188, 190 e 230 Intermediate ETV resistance were present in 27.0% and 15.1% of the samples, according to the Brazilian protocol and to Stanford Db Program, respectively. High-degree of ETV resistance were present in 10 samples (7.9%; IC95% 3.9-14.1), according to the Brazilian protocol Using the Stanford dB Program, 3 out of 126 patients (2.4%; IC95% 3.9-14.1) had high-degree of resistance. Clinical characteristics, number of T CD4 cells and viral load were not predictors to ETV resistance. Conclusions: The presence of at least one mutation potentially associated with decreased virological response to ETV was frequent, in a population highly exposed to NNRTIs. Otherwise high-degree of cross resistance to ETV was not common, suggesting that this drug could be helpful for patients failing to first generation NNRTIs.
publishDate 2010
dc.date.issued.fl_str_mv 2010-07-20
dc.date.accessioned.fl_str_mv 2019-01-16T11:09:26Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv PACHECO, Priscila Ribeiro Guimarães. Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás. 2010. 103 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2010.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/9230
dc.identifier.dark.fl_str_mv ark:/38995/0013000000s3c
identifier_str_mv PACHECO, Priscila Ribeiro Guimarães. Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás. 2010. 103 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2010.
ark:/38995/0013000000s3c
url http://repositorio.bc.ufg.br/tede/handle/tede/9230
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 6085308344741430434
dc.relation.confidence.fl_str_mv 600
600
600
dc.relation.department.fl_str_mv -7769011444564556288
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