Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART.
Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strate...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4725846?pdf=render |
_version_ | 1819090703397945344 |
---|---|
author | Jose Manuel Vazquez-Guillen Gerardo C Palacios-Saucedo Lydia G Rivera-Morales Jorge Garcia-Campos Rocio Ortiz-Lopez Marc Noguera-Julian Roger Paredes Herlinda J Vielma-Ramirez Teresa J Ramirez Marcelino Chavez-Garcia Paulo Lopez-Guillen Evangelina Briones-Lara Luz M Sanchez-Sanchez Carlos A Vazquez-Martinez Cristina Rodriguez-Padilla |
author_facet | Jose Manuel Vazquez-Guillen Gerardo C Palacios-Saucedo Lydia G Rivera-Morales Jorge Garcia-Campos Rocio Ortiz-Lopez Marc Noguera-Julian Roger Paredes Herlinda J Vielma-Ramirez Teresa J Ramirez Marcelino Chavez-Garcia Paulo Lopez-Guillen Evangelina Briones-Lara Luz M Sanchez-Sanchez Carlos A Vazquez-Martinez Cristina Rodriguez-Padilla |
author_sort | Jose Manuel Vazquez-Guillen |
collection | DOAJ |
description | Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI. |
first_indexed | 2024-12-21T22:28:03Z |
format | Article |
id | doaj.art-453c670051a74df98812a3105ff026cc |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-21T22:28:03Z |
publishDate | 2016-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-453c670051a74df98812a3105ff026cc2022-12-21T18:48:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014759110.1371/journal.pone.0147591Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART.Jose Manuel Vazquez-GuillenGerardo C Palacios-SaucedoLydia G Rivera-MoralesJorge Garcia-CamposRocio Ortiz-LopezMarc Noguera-JulianRoger ParedesHerlinda J Vielma-RamirezTeresa J RamirezMarcelino Chavez-GarciaPaulo Lopez-GuillenEvangelina Briones-LaraLuz M Sanchez-SanchezCarlos A Vazquez-MartinezCristina Rodriguez-PadillaAlthough Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI.http://europepmc.org/articles/PMC4725846?pdf=render |
spellingShingle | Jose Manuel Vazquez-Guillen Gerardo C Palacios-Saucedo Lydia G Rivera-Morales Jorge Garcia-Campos Rocio Ortiz-Lopez Marc Noguera-Julian Roger Paredes Herlinda J Vielma-Ramirez Teresa J Ramirez Marcelino Chavez-Garcia Paulo Lopez-Guillen Evangelina Briones-Lara Luz M Sanchez-Sanchez Carlos A Vazquez-Martinez Cristina Rodriguez-Padilla Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. PLoS ONE |
title | Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. |
title_full | Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. |
title_fullStr | Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. |
title_full_unstemmed | Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. |
title_short | Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART. |
title_sort | mutations related to antiretroviral resistance identified by ultra deep sequencing in hiv 1 infected children under structured interruptions of haart |
url | http://europepmc.org/articles/PMC4725846?pdf=render |
work_keys_str_mv | AT josemanuelvazquezguillen mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT gerardocpalaciossaucedo mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT lydiagriveramorales mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT jorgegarciacampos mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT rocioortizlopez mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT marcnoguerajulian mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT rogerparedes mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT herlindajvielmaramirez mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT teresajramirez mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT marcelinochavezgarcia mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT paulolopezguillen mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT evangelinabrioneslara mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT luzmsanchezsanchez mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT carlosavazquezmartinez mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart AT cristinarodriguezpadilla mutationsrelatedtoantiretroviralresistanceidentifiedbyultradeepsequencinginhiv1infectedchildrenunderstructuredinterruptionsofhaart |