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A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load

BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL) in treatment-naïve (TN) and treatment-experienced (TE) individuals infected with HIV-1 in Québec, Canada, between...

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Autores principales: Charest, Hugues, Doualla-Bell, Florence, Cantin, Régis, Murphy, Donald G., Lemieux, Linda, Brenner, Bluma, Hardy, Isabelle, Moisi, Daniela, Lo, Ernest, Baril, Jean-Guy, Wainberg, Mark A., Roger, Michel, Tremblay, Cécile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190276/
https://www.ncbi.nlm.nih.gov/pubmed/25295725
http://dx.doi.org/10.1371/journal.pone.0109420
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author Charest, Hugues
Doualla-Bell, Florence
Cantin, Régis
Murphy, Donald G.
Lemieux, Linda
Brenner, Bluma
Hardy, Isabelle
Moisi, Daniela
Lo, Ernest
Baril, Jean-Guy
Wainberg, Mark A.
Roger, Michel
Tremblay, Cécile
author_facet Charest, Hugues
Doualla-Bell, Florence
Cantin, Régis
Murphy, Donald G.
Lemieux, Linda
Brenner, Bluma
Hardy, Isabelle
Moisi, Daniela
Lo, Ernest
Baril, Jean-Guy
Wainberg, Mark A.
Roger, Michel
Tremblay, Cécile
author_sort Charest, Hugues
collection PubMed
description BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL) in treatment-naïve (TN) and treatment-experienced (TE) individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%)], nucleoside [NRTI (from 78% to 37%) and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%)] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004). CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant variants.
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spelling pubmed-41902762014-10-10 A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load Charest, Hugues Doualla-Bell, Florence Cantin, Régis Murphy, Donald G. Lemieux, Linda Brenner, Bluma Hardy, Isabelle Moisi, Daniela Lo, Ernest Baril, Jean-Guy Wainberg, Mark A. Roger, Michel Tremblay, Cécile PLoS One Research Article BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL) in treatment-naïve (TN) and treatment-experienced (TE) individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%)], nucleoside [NRTI (from 78% to 37%) and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%)] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004). CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant variants. Public Library of Science 2014-10-08 /pmc/articles/PMC4190276/ /pubmed/25295725 http://dx.doi.org/10.1371/journal.pone.0109420 Text en © 2014 Charest et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Charest, Hugues
Doualla-Bell, Florence
Cantin, Régis
Murphy, Donald G.
Lemieux, Linda
Brenner, Bluma
Hardy, Isabelle
Moisi, Daniela
Lo, Ernest
Baril, Jean-Guy
Wainberg, Mark A.
Roger, Michel
Tremblay, Cécile
A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load
title A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load
title_full A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load
title_fullStr A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load
title_full_unstemmed A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load
title_short A Significant Reduction in the Frequency of HIV-1 Drug Resistance in Québec from 2001 to 2011 Is Associated with a Decrease in the Monitored Viral Load
title_sort significant reduction in the frequency of hiv-1 drug resistance in québec from 2001 to 2011 is associated with a decrease in the monitored viral load
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190276/
https://www.ncbi.nlm.nih.gov/pubmed/25295725
http://dx.doi.org/10.1371/journal.pone.0109420
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