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Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals

OBJECTIVES: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission sou...

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Autores principales: Winand, Raf, Theys, Kristof, Eusébio, Mónica, Aerts, Jan, Camacho, Ricardo J., Gomes, Perpetua, Suchard, Marc A., Vandamme, Anne-Mieke, Abecasis, Ana B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570689/
https://www.ncbi.nlm.nih.gov/pubmed/26355575
http://dx.doi.org/10.1097/QAD.0000000000000811
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author Winand, Raf
Theys, Kristof
Eusébio, Mónica
Aerts, Jan
Camacho, Ricardo J.
Gomes, Perpetua
Suchard, Marc A.
Vandamme, Anne-Mieke
Abecasis, Ana B.
author_facet Winand, Raf
Theys, Kristof
Eusébio, Mónica
Aerts, Jan
Camacho, Ricardo J.
Gomes, Perpetua
Suchard, Marc A.
Vandamme, Anne-Mieke
Abecasis, Ana B.
author_sort Winand, Raf
collection PubMed
description OBJECTIVES: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. DESIGN: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. METHODS: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. RESULTS: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers – above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. CONCLUSION: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients.
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spelling pubmed-45706892015-09-30 Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals Winand, Raf Theys, Kristof Eusébio, Mónica Aerts, Jan Camacho, Ricardo J. Gomes, Perpetua Suchard, Marc A. Vandamme, Anne-Mieke Abecasis, Ana B. AIDS Concise Communication OBJECTIVES: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. DESIGN: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. METHODS: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. RESULTS: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers – above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. CONCLUSION: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients. Lippincott Williams & Wilkins 2015-09-24 2015-09-24 /pmc/articles/PMC4570689/ /pubmed/26355575 http://dx.doi.org/10.1097/QAD.0000000000000811 Text en Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
spellingShingle Concise Communication
Winand, Raf
Theys, Kristof
Eusébio, Mónica
Aerts, Jan
Camacho, Ricardo J.
Gomes, Perpetua
Suchard, Marc A.
Vandamme, Anne-Mieke
Abecasis, Ana B.
Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals
title Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals
title_full Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals
title_fullStr Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals
title_full_unstemmed Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals
title_short Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals
title_sort assessing transmissibility of hiv-1 drug resistance mutations from treated and from drug-naive individuals
topic Concise Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570689/
https://www.ncbi.nlm.nih.gov/pubmed/26355575
http://dx.doi.org/10.1097/QAD.0000000000000811
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