Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/3301 |
Resumo: | Among pregnant women infected with HIV-1, drug resistance mutations to antiretroviral drugs (ARV) represent a challenge for the prevention to HIV-1 mother-to child-transmission (MTCT) and for future maternal treatment options. The goal of this study was to assess the presence of mutations in gp41 associated with natural resistance to the fusion inhibitor T-20, polymorphisms and HIV-1 subtypes among pregnant women never treated with T-20 and under different exposure levels to other ARV. A total of 153 pregnant women infected with HIV-1 (ARV naive, under MTCT prophylaxis or under ARV treatment/HAART) was recruited from june/2008-june/2010. The env gene gp41 fragment of 766 bp (FP, HR1, HR2, TM regions) was amplified by “nested”-PCR from cDNA and sequenced among 110 patients (Big Dye Terminator Sequencing v. 3.1, Applied Biosystems, EUA; ABI Prism 3130). HIV-1 subtypes were assigned by REGA tool and by phylogenetic analyses (Neighbor-Joining, Kimura 2-P). T-20 resistance mutations were analyzed according to the IAS/USA, Stanford online HIV Drug Resistance Database and other sources. The median age of pregnant women (n=110) was 26 years (16-42 years), 16% were AIDS cases. The frequency of natural resistance (N42D, L44M and R46M) to T-20 was 5.4% (6/110). All resistance mutations were identified in HIV-1 subtype B isolates within the HR1 region of the gp41 fragment. The prevalence of compensatory mutations in HR2 region of gp41 was 20.9% (23/110): S138A (n=11), E137K (n=10) e N126K (n=2). All 110 isolates presented several polymorphisms. The following polymorphisms were observed in FP of gp41: M24I/L/V, I7M/V, and I4A/F/L/M. In 42.7% (47/110) of isolates many indels within the gp41 FP fragment were observed. Polymorphisms identified in HR1 were: K77E/L/Q/R/V, I69V, L54M, R46K/Q, N42S and Q32L/N. Polymorphisms in HR2 gp41 region were: S157D/N, E151A/K/Q, E148D, I135L, S133D/E/N/Q/R/T, H132F/Y, L130E/I/T, S129D/G/N/Q, N125A/D/E/S, R122K, N121E/D and E119Q. Moderate rate of natural resistance for T-20 and higher prevalence of polymorphisms in env gp41 region were described. Moreover higher prevalence of HIV-1 “non- B subtypes” C and F1 was observed. These molecular data may contribute to better therapeutic and MTCT preventive strategies for pregnant women infected with HIV-1. |
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Stefani, Mariane Martins de Araújohttp://lattes.cnpq.br/5581414958714905Cardoso, Ludimila Paula VazStefani, Mariane Martins de AraújoKipnis, AndréFonseca, Simone Gonçalves dahttp://lattes.cnpq.br/0634003740853760Reis, Mônica Nogueira da Guarda2014-10-09T11:13:03Z2013-02-25REIS, Mônica Nogueira da Guarda. Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás. 2013. 98 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, 2013.http://repositorio.bc.ufg.br/tede/handle/tede/3301Among pregnant women infected with HIV-1, drug resistance mutations to antiretroviral drugs (ARV) represent a challenge for the prevention to HIV-1 mother-to child-transmission (MTCT) and for future maternal treatment options. The goal of this study was to assess the presence of mutations in gp41 associated with natural resistance to the fusion inhibitor T-20, polymorphisms and HIV-1 subtypes among pregnant women never treated with T-20 and under different exposure levels to other ARV. A total of 153 pregnant women infected with HIV-1 (ARV naive, under MTCT prophylaxis or under ARV treatment/HAART) was recruited from june/2008-june/2010. The env gene gp41 fragment of 766 bp (FP, HR1, HR2, TM regions) was amplified by “nested”-PCR from cDNA and sequenced among 110 patients (Big Dye Terminator Sequencing v. 3.1, Applied Biosystems, EUA; ABI Prism 3130). HIV-1 subtypes were assigned by REGA tool and by phylogenetic analyses (Neighbor-Joining, Kimura 2-P). T-20 resistance mutations were analyzed according to the IAS/USA, Stanford online HIV Drug Resistance Database and other sources. The median age of pregnant women (n=110) was 26 years (16-42 years), 16% were AIDS cases. The frequency of natural resistance (N42D, L44M and R46M) to T-20 was 5.4% (6/110). All resistance mutations were identified in HIV-1 subtype B isolates within the HR1 region of the gp41 fragment. The prevalence of compensatory mutations in HR2 region of gp41 was 20.9% (23/110): S138A (n=11), E137K (n=10) e N126K (n=2). All 110 isolates presented several polymorphisms. The following polymorphisms were observed in FP of gp41: M24I/L/V, I7M/V, and I4A/F/L/M. In 42.7% (47/110) of isolates many indels within the gp41 FP fragment were observed. Polymorphisms identified in HR1 were: K77E/L/Q/R/V, I69V, L54M, R46K/Q, N42S and Q32L/N. Polymorphisms in HR2 gp41 region were: S157D/N, E151A/K/Q, E148D, I135L, S133D/E/N/Q/R/T, H132F/Y, L130E/I/T, S129D/G/N/Q, N125A/D/E/S, R122K, N121E/D and E119Q. Moderate rate of natural resistance for T-20 and higher prevalence of polymorphisms in env gp41 region were described. Moreover higher prevalence of HIV-1 “non- B subtypes” C and F1 was observed. These molecular data may contribute to better therapeutic and MTCT preventive strategies for pregnant women infected with HIV-1.Nas gestantes infectadas pelo HIV-1, a presença de mutações associadas à resistência aos antirretrovirais (ARV) representa um desafio para a prevenção da transmissão materno-infantil do HIV-1 e para futuras opções de tratamento materno. Este estudo teve como objetivo avaliar a presença de mutações na gp41 associadas à resistência natural ao inibidor de fusão T-20, polimorfismos e subtipos do HIV-1 em gestantes nunca tratadas com T-20 e com diferentes níveis de exposição a outros ARVs. Um total de 153 gestantes infectadas pelo HIV-1 (virgens de tratamento ARV, em profilaxia para TV ou em tratamento com ARV) foi recrutado entre junho/2008-junho/2010. O fragmento de 766 pb da gp41 do gene env (porções PF, HR1, HR2 e TM) foi amplificado por “nested”-PCR a partir de cDNA e sequenciado em 110 pacientes (Big Dye Terminator Sequencing v. 3.1, Applied Biosystems, EUA; ABI Prism 3130). Os subtipos do HIV-1 foram identificados pelos softwares REGA HIV-1 e por inferência filogenética (Neighbor-Joining, Kimura 2-P). Mutações associadas à resistência natural ao T-20 foram analisadas por comparação com o banco de dados da IAS-USA, Stanford HIV Drug Resistance Database e outras fontes. A mediana de idade das gestantes (n=110) foi de 26 anos (variação 16-42 anos), 16% eram casos sintomáticos. Mutações associadas à resistência natural para T-20 (N42D, L44M, R46M) foram encontradas em 5,4% (6/110). Todas as mutações associadas à resistência foram descritas nos isolados do subtipo B no fragmento HR1 da gp41. A prevalência de mutações compensatórias foi de 20,9% (23/110): S138A (n=11), E137K (n=10) e N126K (n=2). Todos os 110 isolados apresentaram vários polimorfismos. Os polimorfismos encontrados no fragmento PF da gp41 foram: M24I/L/V, I7M/V e I4A/F/L/M. Em 42,7% (47/110) dos isolados apresentaram várias inserções e deleções dentro do fragmento FP da gp41. Os polimorfismos na região HR1 foram: K77E/L/Q/R/V, I69V, L54M, R46K/Q, N42S e Q32L/N. Polimorfismos na região HR2 da gp41 foram: S157D/N, E151A/K/Q, E148D, I135L, S133D/E/N/Q/R/T, H132F/Y, L130E/I/T, S129D/G/N/Q, N125A/D/E/S, R122K, N121E/D e E119Q. Moderada prevalência de resistência natural ao T-20 e elevada frequência de polimorfismos na região da gp41 foram descritas. Além disso, uma alta prevalência de “subtipos não-B” C e F1 de HIV-1 foram observados. Estes dados moleculares podem contribuir para estratégias terapêuticas e profiláticas mais eficazes para gestantes infectadas pelo HIV-1.Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2014-10-08T21:49:25Z No. of bitstreams: 2 Dissertação de Mestrado Mônica Reis19_07.d oc.pdf: 1532492 bytes, checksum: b88a88ff0daba799bc2fd5e3082c7928 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-10-09T11:13:03Z (GMT) No. of bitstreams: 2 Dissertação de Mestrado Mônica Reis19_07.d oc.pdf: 1532492 bytes, checksum: b88a88ff0daba799bc2fd5e3082c7928 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-10-09T11:13:03Z (GMT). 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dc.title.por.fl_str_mv |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
dc.title.alternative.eng.fl_str_mv |
Natural resistance to T-20 among pregnant women infected with HIV-1 from central western Brazil |
title |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
spellingShingle |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás Reis, Mônica Nogueira da Guarda Gestantes HIV-1 Enfuvirtida Pregnant Enfuvirtide Pregnant women HIV-1 CIENCIAS BIOLOGICAS::MICROBIOLOGIA |
title_short |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
title_full |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
title_fullStr |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
title_full_unstemmed |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
title_sort |
Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás |
author |
Reis, Mônica Nogueira da Guarda |
author_facet |
Reis, Mônica Nogueira da Guarda |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Stefani, Mariane Martins de Araújo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5581414958714905 |
dc.contributor.advisor-co1.fl_str_mv |
Cardoso, Ludimila Paula Vaz |
dc.contributor.referee1.fl_str_mv |
Stefani, Mariane Martins de Araújo |
dc.contributor.referee2.fl_str_mv |
Kipnis, André |
dc.contributor.referee3.fl_str_mv |
Fonseca, Simone Gonçalves da |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0634003740853760 |
dc.contributor.author.fl_str_mv |
Reis, Mônica Nogueira da Guarda |
contributor_str_mv |
Stefani, Mariane Martins de Araújo Cardoso, Ludimila Paula Vaz Stefani, Mariane Martins de Araújo Kipnis, André Fonseca, Simone Gonçalves da |
dc.subject.por.fl_str_mv |
Gestantes HIV-1 Enfuvirtida Pregnant Enfuvirtide |
topic |
Gestantes HIV-1 Enfuvirtida Pregnant Enfuvirtide Pregnant women HIV-1 CIENCIAS BIOLOGICAS::MICROBIOLOGIA |
dc.subject.eng.fl_str_mv |
Pregnant women HIV-1 |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::MICROBIOLOGIA |
description |
Among pregnant women infected with HIV-1, drug resistance mutations to antiretroviral drugs (ARV) represent a challenge for the prevention to HIV-1 mother-to child-transmission (MTCT) and for future maternal treatment options. The goal of this study was to assess the presence of mutations in gp41 associated with natural resistance to the fusion inhibitor T-20, polymorphisms and HIV-1 subtypes among pregnant women never treated with T-20 and under different exposure levels to other ARV. A total of 153 pregnant women infected with HIV-1 (ARV naive, under MTCT prophylaxis or under ARV treatment/HAART) was recruited from june/2008-june/2010. The env gene gp41 fragment of 766 bp (FP, HR1, HR2, TM regions) was amplified by “nested”-PCR from cDNA and sequenced among 110 patients (Big Dye Terminator Sequencing v. 3.1, Applied Biosystems, EUA; ABI Prism 3130). HIV-1 subtypes were assigned by REGA tool and by phylogenetic analyses (Neighbor-Joining, Kimura 2-P). T-20 resistance mutations were analyzed according to the IAS/USA, Stanford online HIV Drug Resistance Database and other sources. The median age of pregnant women (n=110) was 26 years (16-42 years), 16% were AIDS cases. The frequency of natural resistance (N42D, L44M and R46M) to T-20 was 5.4% (6/110). All resistance mutations were identified in HIV-1 subtype B isolates within the HR1 region of the gp41 fragment. The prevalence of compensatory mutations in HR2 region of gp41 was 20.9% (23/110): S138A (n=11), E137K (n=10) e N126K (n=2). All 110 isolates presented several polymorphisms. The following polymorphisms were observed in FP of gp41: M24I/L/V, I7M/V, and I4A/F/L/M. In 42.7% (47/110) of isolates many indels within the gp41 FP fragment were observed. Polymorphisms identified in HR1 were: K77E/L/Q/R/V, I69V, L54M, R46K/Q, N42S and Q32L/N. Polymorphisms in HR2 gp41 region were: S157D/N, E151A/K/Q, E148D, I135L, S133D/E/N/Q/R/T, H132F/Y, L130E/I/T, S129D/G/N/Q, N125A/D/E/S, R122K, N121E/D and E119Q. Moderate rate of natural resistance for T-20 and higher prevalence of polymorphisms in env gp41 region were described. Moreover higher prevalence of HIV-1 “non- B subtypes” C and F1 was observed. These molecular data may contribute to better therapeutic and MTCT preventive strategies for pregnant women infected with HIV-1. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-02-25 |
dc.date.accessioned.fl_str_mv |
2014-10-09T11:13:03Z |
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 |
REIS, Mônica Nogueira da Guarda. Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás. 2013. 98 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, 2013. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/3301 |
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REIS, Mônica Nogueira da Guarda. Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás. 2013. 98 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, 2013. |
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http://repositorio.bc.ufg.br/tede/handle/tede/3301 |
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por |
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por |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP) |
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UFG |
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Brasil |
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Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) |
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Universidade Federal de Goiás |
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