The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors

Detalhes bibliográficos
Autor(a) principal: Santos,André FA
Data de Publicação: 2011
Outros Autores: Soares,Marcelo A
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Memórias do Instituto Oswaldo Cruz
Texto Completo: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200010
Resumo: The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations.
id FIOCRUZ-4_dc57a2e86e5203ccb3fd82f284a2a5c0
oai_identifier_str oai:scielo:S0074-02762011000200010
network_acronym_str FIOCRUZ-4
network_name_str Memórias do Instituto Oswaldo Cruz
spelling The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitorsD30Nhypersusceptibilityphenotypingdrug resistanceprotease inhibitorsN88DThe human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations.Instituto Oswaldo Cruz, Ministério da Saúde2011-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200010Memórias do Instituto Oswaldo Cruz v.106 n.2 2011reponame:Memórias do Instituto Oswaldo Cruzinstname:Fundação Oswaldo Cruzinstacron:FIOCRUZ10.1590/S0074-02762011000200010info:eu-repo/semantics/openAccessSantos,André FASoares,Marcelo Aeng2020-04-25T17:50:57Zhttp://www.scielo.br/oai/scielo-oai.php0074-02761678-8060opendoar:null2020-04-26 02:17:30.902Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruztrue
dc.title.none.fl_str_mv The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
title The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
spellingShingle The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
Santos,André FA
D30N
hypersusceptibility
phenotyping
drug resistance
protease inhibitors
N88D
title_short The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
title_full The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
title_fullStr The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
title_full_unstemmed The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
title_sort The impact of the nelfinavir resistance-conferring mutation D30N on the susceptibility of HIV-1 subtype B to other protease inhibitors
author Santos,André FA
author_facet Santos,André FA
Soares,Marcelo A
author_role author
author2 Soares,Marcelo A
author2_role author
dc.contributor.author.fl_str_mv Santos,André FA
Soares,Marcelo A
dc.subject.por.fl_str_mv D30N
hypersusceptibility
phenotyping
drug resistance
protease inhibitors
N88D
topic D30N
hypersusceptibility
phenotyping
drug resistance
protease inhibitors
N88D
dc.description.none.fl_txt_mv The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations.
description The human immunodeficiency virus type 1 (HIV-1) protease mutation D30N is exclusively selected by the protease inhibitor (PI) nelfinavir and confers resistance to this drug. We demonstrate that D30N increases the susceptibility to saquinavir (SQV) and amprenavir in HIV-1 subtype B isolates and that the N88D mutation in a D30N background neutralizes this effect. D30N also suppresses indinavir (IDV) resistance caused by the M46I mutation. Interestingly, in patients with viruses originally containing the D30N mutation who were treated with IDV or SQV, the virus either reversed this mutation or acquired N88D, suggesting an antagonistic effect of D30N upon exposure to these PIs. These findings can improve direct salvage drug treatment in resource limited countries where subtype B is epidemiologically important and extend the value of first and second line PIs in these populations.
publishDate 2011
dc.date.none.fl_str_mv 2011-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200010
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762011000200010
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0074-02762011000200010
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
dc.source.none.fl_str_mv Memórias do Instituto Oswaldo Cruz v.106 n.2 2011
reponame:Memórias do Instituto Oswaldo Cruz
instname:Fundação Oswaldo Cruz
instacron:FIOCRUZ
reponame_str Memórias do Instituto Oswaldo Cruz
collection Memórias do Instituto Oswaldo Cruz
instname_str Fundação Oswaldo Cruz
instacron_str FIOCRUZ
institution FIOCRUZ
repository.name.fl_str_mv Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruz
repository.mail.fl_str_mv
_version_ 1669937708906053632

Registros relacionados