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Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure

BACKGROUND: In our study, we have hypothesized that proviral DNA may show the history of mutations that emerged at previous failures to a Raltegravir containing regimen, in patients who are currently undetectable and candidates to simplification to a Dolutegravir containing regimen, in order to deci...

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Autores principales: Fernández-Caballero, Jose Ángel, Chueca, Natalia, Álvarez, Marta, Mérida, María Dolores, López, Josefa, Sánchez, José Antonio, Vinuesa, David, Martínez, María Ángeles, Hernández, José, García, Federico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866296/
https://www.ncbi.nlm.nih.gov/pubmed/27177767
http://dx.doi.org/10.1186/s12879-016-1545-8
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author Fernández-Caballero, Jose Ángel
Chueca, Natalia
Álvarez, Marta
Mérida, María Dolores
López, Josefa
Sánchez, José Antonio
Vinuesa, David
Martínez, María Ángeles
Hernández, José
García, Federico
author_facet Fernández-Caballero, Jose Ángel
Chueca, Natalia
Álvarez, Marta
Mérida, María Dolores
López, Josefa
Sánchez, José Antonio
Vinuesa, David
Martínez, María Ángeles
Hernández, José
García, Federico
author_sort Fernández-Caballero, Jose Ángel
collection PubMed
description BACKGROUND: In our study, we have hypothesized that proviral DNA may show the history of mutations that emerged at previous failures to a Raltegravir containing regimen, in patients who are currently undetectable and candidates to simplification to a Dolutegravir containing regimen, in order to decide on once a day or twice a day dosing. METHODS: We have performed a pilot, observational, retrospective, non interventional study, including 7 patients infected by HIV-1, all with a history of previous failure to a RAL containing regimen, that were successfully salvaged and had reached viral suppression. A genotypic viral Integrase region study was available for each patient at the moment of RAL failure. After an average (IQR) time of 48 months (29–53) Integrase resistance mutations in proviral DNA were studied. RESULTS: All the patients were infected by HIV-1 B subtypes, with a mean age of 55 (range 43 to 56), originating from Spain, and 4 were women. Median viral load (log) and CD4 count at the moment of the study on proviral DNA was of 1.3 log cp/ml (range 0–1.47) and 765.5 cells/μL (range; 436.75–1023.75). The median time (IQR) between previous failure to RAL and the study on proviral DNA was 48 (29–53) months. At Raltegravir failure, N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). In proviral DNA, N155H was detected by population sequencing in three patients (42.8 %), and UDS demonstrated a 9.77 % relative abundance of N155H in the remaining patient. Sanger sequencing correctly identified all the secondary mutations. CONCLUSION: This is a pilot study that demonstrates the possibility of properly identifying N155H and some secondary mutations 29–53 months after failure.
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spelling pubmed-48662962016-05-31 Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure Fernández-Caballero, Jose Ángel Chueca, Natalia Álvarez, Marta Mérida, María Dolores López, Josefa Sánchez, José Antonio Vinuesa, David Martínez, María Ángeles Hernández, José García, Federico BMC Infect Dis Research Article BACKGROUND: In our study, we have hypothesized that proviral DNA may show the history of mutations that emerged at previous failures to a Raltegravir containing regimen, in patients who are currently undetectable and candidates to simplification to a Dolutegravir containing regimen, in order to decide on once a day or twice a day dosing. METHODS: We have performed a pilot, observational, retrospective, non interventional study, including 7 patients infected by HIV-1, all with a history of previous failure to a RAL containing regimen, that were successfully salvaged and had reached viral suppression. A genotypic viral Integrase region study was available for each patient at the moment of RAL failure. After an average (IQR) time of 48 months (29–53) Integrase resistance mutations in proviral DNA were studied. RESULTS: All the patients were infected by HIV-1 B subtypes, with a mean age of 55 (range 43 to 56), originating from Spain, and 4 were women. Median viral load (log) and CD4 count at the moment of the study on proviral DNA was of 1.3 log cp/ml (range 0–1.47) and 765.5 cells/μL (range; 436.75–1023.75). The median time (IQR) between previous failure to RAL and the study on proviral DNA was 48 (29–53) months. At Raltegravir failure, N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). In proviral DNA, N155H was detected by population sequencing in three patients (42.8 %), and UDS demonstrated a 9.77 % relative abundance of N155H in the remaining patient. Sanger sequencing correctly identified all the secondary mutations. CONCLUSION: This is a pilot study that demonstrates the possibility of properly identifying N155H and some secondary mutations 29–53 months after failure. BioMed Central 2016-05-13 /pmc/articles/PMC4866296/ /pubmed/27177767 http://dx.doi.org/10.1186/s12879-016-1545-8 Text en © Fernández-Caballero et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fernández-Caballero, Jose Ángel
Chueca, Natalia
Álvarez, Marta
Mérida, María Dolores
López, Josefa
Sánchez, José Antonio
Vinuesa, David
Martínez, María Ángeles
Hernández, José
García, Federico
Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
title Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
title_full Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
title_fullStr Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
title_full_unstemmed Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
title_short Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
title_sort usefulness of integrase resistance testing in proviral hiv-1 dna in patients with raltegravir prior failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866296/
https://www.ncbi.nlm.nih.gov/pubmed/27177767
http://dx.doi.org/10.1186/s12879-016-1545-8
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