Cargando…

Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure

We describe drug-resistance mutation dynamics of the gag gene among individuals under antiretroviral virologic failure who underwent analytical treatment interruption (ATI). These mutations occur in and around the cleavage sites that form the particles that become the mature HIV-1 virus. The study i...

Descripción completa

Detalles Bibliográficos
Autores principales: Hunter, James R., dos Santos, Domingos E. Matos, Munerato, Patricia, Janini, Luiz Mario, Castelo, Adauto, Sucupira, Maria Cecilia, Truong, Hong-Ha M., Diaz, Ricardo Sobhie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145614/
https://www.ncbi.nlm.nih.gov/pubmed/35631055
http://dx.doi.org/10.3390/pathogens11050534
_version_ 1784716357143625728
author Hunter, James R.
dos Santos, Domingos E. Matos
Munerato, Patricia
Janini, Luiz Mario
Castelo, Adauto
Sucupira, Maria Cecilia
Truong, Hong-Ha M.
Diaz, Ricardo Sobhie
author_facet Hunter, James R.
dos Santos, Domingos E. Matos
Munerato, Patricia
Janini, Luiz Mario
Castelo, Adauto
Sucupira, Maria Cecilia
Truong, Hong-Ha M.
Diaz, Ricardo Sobhie
author_sort Hunter, James R.
collection PubMed
description We describe drug-resistance mutation dynamics of the gag gene among individuals under antiretroviral virologic failure who underwent analytical treatment interruption (ATI). These mutations occur in and around the cleavage sites that form the particles that become the mature HIV-1 virus. The study involved a 12-week interruption in antiretroviral therapy (ART) and sequencing of the gag gene in 38 individuals experiencing virologic failure and harboring triple-class resistant HIV strains. Regions of the gag gene surrounding the NC-p2 and p1-p6 cleavage sites were sequenced at baseline before ATI and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Fourteen of the sixteen patients sequenced presented at least one mutation in the gag gene at baseline, with an average of 4.93 mutations per patient. All the mutations had reverted to the wild type by the end of the study. Mutations in the gag gene complement mutations in the pol gene to restore HIV fitness. Those mutations around cleavage sites and within substrates contribute to protease inhibitor resistance and difficulty in re-establishing effective virologic suppression. ART interruption in the presence of antiretroviral resistant HIV strains was used here as a practical measure for more adapted HIV profiles in the absence of ART selective pressure.
format Online
Article
Text
id pubmed-9145614
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91456142022-05-29 Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure Hunter, James R. dos Santos, Domingos E. Matos Munerato, Patricia Janini, Luiz Mario Castelo, Adauto Sucupira, Maria Cecilia Truong, Hong-Ha M. Diaz, Ricardo Sobhie Pathogens Article We describe drug-resistance mutation dynamics of the gag gene among individuals under antiretroviral virologic failure who underwent analytical treatment interruption (ATI). These mutations occur in and around the cleavage sites that form the particles that become the mature HIV-1 virus. The study involved a 12-week interruption in antiretroviral therapy (ART) and sequencing of the gag gene in 38 individuals experiencing virologic failure and harboring triple-class resistant HIV strains. Regions of the gag gene surrounding the NC-p2 and p1-p6 cleavage sites were sequenced at baseline before ATI and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Fourteen of the sixteen patients sequenced presented at least one mutation in the gag gene at baseline, with an average of 4.93 mutations per patient. All the mutations had reverted to the wild type by the end of the study. Mutations in the gag gene complement mutations in the pol gene to restore HIV fitness. Those mutations around cleavage sites and within substrates contribute to protease inhibitor resistance and difficulty in re-establishing effective virologic suppression. ART interruption in the presence of antiretroviral resistant HIV strains was used here as a practical measure for more adapted HIV profiles in the absence of ART selective pressure. MDPI 2022-05-03 /pmc/articles/PMC9145614/ /pubmed/35631055 http://dx.doi.org/10.3390/pathogens11050534 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hunter, James R.
dos Santos, Domingos E. Matos
Munerato, Patricia
Janini, Luiz Mario
Castelo, Adauto
Sucupira, Maria Cecilia
Truong, Hong-Ha M.
Diaz, Ricardo Sobhie
Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure
title Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure
title_full Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure
title_fullStr Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure
title_full_unstemmed Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure
title_short Antiretroviral Drug-Resistance Mutations on the Gag Gene: Mutation Dynamics during Analytic Treatment Interruption among Individuals Experiencing Virologic Failure
title_sort antiretroviral drug-resistance mutations on the gag gene: mutation dynamics during analytic treatment interruption among individuals experiencing virologic failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145614/
https://www.ncbi.nlm.nih.gov/pubmed/35631055
http://dx.doi.org/10.3390/pathogens11050534
work_keys_str_mv AT hunterjamesr antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT dossantosdomingosematos antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT muneratopatricia antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT janiniluizmario antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT casteloadauto antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT sucupiramariacecilia antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT truonghongham antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure
AT diazricardosobhie antiretroviraldrugresistancemutationsonthegaggenemutationdynamicsduringanalytictreatmentinterruptionamongindividualsexperiencingvirologicfailure