DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS

The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.

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Main Authors: Arruda,Liã Bárbara, Araújo,Marilia Ladeira de, Martinez,Maira Luccia, Gonsalez,Claudio Roberto, Duarte,Alberto José da Silva, Coakley,Eoin, Lie,Yolanda, Casseb,Jorge
Format: Digital revista
Language:English
Published: Instituto de Medicina Tropical de São Paulo 2014
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0036-46652014000400287
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spelling oai:scielo:S0036-466520140004002872014-08-15DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTSArruda,Liã BárbaraAraújo,Marilia Ladeira deMartinez,Maira LucciaGonsalez,Claudio RobertoDuarte,Alberto José da SilvaCoakley,EoinLie,YolandaCasseb,Jorge HIV-1 Tropism Brazil V3 loop The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.info:eu-repo/semantics/openAccessInstituto de Medicina Tropical de São PauloRevista do Instituto de Medicina Tropical de São Paulo v.56 n.4 20142014-08-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0036-46652014000400287en10.1590/S0036-46652014000400003
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language English
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author Arruda,Liã Bárbara
Araújo,Marilia Ladeira de
Martinez,Maira Luccia
Gonsalez,Claudio Roberto
Duarte,Alberto José da Silva
Coakley,Eoin
Lie,Yolanda
Casseb,Jorge
spellingShingle Arruda,Liã Bárbara
Araújo,Marilia Ladeira de
Martinez,Maira Luccia
Gonsalez,Claudio Roberto
Duarte,Alberto José da Silva
Coakley,Eoin
Lie,Yolanda
Casseb,Jorge
DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS
author_facet Arruda,Liã Bárbara
Araújo,Marilia Ladeira de
Martinez,Maira Luccia
Gonsalez,Claudio Roberto
Duarte,Alberto José da Silva
Coakley,Eoin
Lie,Yolanda
Casseb,Jorge
author_sort Arruda,Liã Bárbara
title DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS
title_short DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS
title_full DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS
title_fullStr DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS
title_full_unstemmed DETERMINATION OF VIRAL TROPISM BY GENOTYPING AND PHENOTYPING ASSAYS IN BRAZILIAN HIV-1-INFECTED PATIENTS
title_sort determination of viral tropism by genotyping and phenotyping assays in brazilian hiv-1-infected patients
description The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.
publisher Instituto de Medicina Tropical de São Paulo
publishDate 2014
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0036-46652014000400287
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