Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc.
<h4>Objectives</h4>We analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.<h4>Methods</h4>87 RNA and 60 DNA samples were used. The viral tropism was predicted using the ge...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0125502 |
| _version_ | 1819140220489039872 |
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| author | Saleta Sierra J Nikolai Dybowski Alejandro Pironti Dominik Heider Lisa Güney Alex Thielen Stefan Reuter Stefan Esser Gerd Fätkenheuer Thomas Lengauer Daniel Hoffmann Herbert Pfister Björn Jensen Rolf Kaiser |
| author_facet | Saleta Sierra J Nikolai Dybowski Alejandro Pironti Dominik Heider Lisa Güney Alex Thielen Stefan Reuter Stefan Esser Gerd Fätkenheuer Thomas Lengauer Daniel Hoffmann Herbert Pfister Björn Jensen Rolf Kaiser |
| author_sort | Saleta Sierra |
| collection | DOAJ |
| description | <h4>Objectives</h4>We analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.<h4>Methods</h4>87 RNA and 60 DNA samples were used. The viral tropism was predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in triplicate, 43 samples with the ESTA assay and 45 with next-generation sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC-resistance mutations on clinical outcome was also studied.<h4>Results</h4>Concordance between single-amplification testing compared to ESTA and to NGS was in the order of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of baseline R5 viruses in RNA and DNA samples by all methods significantly correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC. No influence of the GSS or MVC-resistance mutations but adherence to treatment, on the clinical outcome was detected.<h4>Conclusions</h4>Proviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug. In addition, the new prediction system T-CUP produced reliable results. |
| first_indexed | 2024-12-22T11:35:06Z |
| format | Article |
| id | doaj.art-d487bf5b77f046c6baf74d10d55f6529 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:35:06Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d487bf5b77f046c6baf74d10d55f65292022-12-21T18:27:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012550210.1371/journal.pone.0125502Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc.Saleta SierraJ Nikolai DybowskiAlejandro PirontiDominik HeiderLisa GüneyAlex ThielenStefan ReuterStefan EsserGerd FätkenheuerThomas LengauerDaniel HoffmannHerbert PfisterBjörn JensenRolf Kaiser<h4>Objectives</h4>We analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.<h4>Methods</h4>87 RNA and 60 DNA samples were used. The viral tropism was predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in triplicate, 43 samples with the ESTA assay and 45 with next-generation sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC-resistance mutations on clinical outcome was also studied.<h4>Results</h4>Concordance between single-amplification testing compared to ESTA and to NGS was in the order of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of baseline R5 viruses in RNA and DNA samples by all methods significantly correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC. No influence of the GSS or MVC-resistance mutations but adherence to treatment, on the clinical outcome was detected.<h4>Conclusions</h4>Proviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug. In addition, the new prediction system T-CUP produced reliable results.https://doi.org/10.1371/journal.pone.0125502 |
| spellingShingle | Saleta Sierra J Nikolai Dybowski Alejandro Pironti Dominik Heider Lisa Güney Alex Thielen Stefan Reuter Stefan Esser Gerd Fätkenheuer Thomas Lengauer Daniel Hoffmann Herbert Pfister Björn Jensen Rolf Kaiser Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc. PLoS ONE |
| title | Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc. |
| title_full | Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc. |
| title_fullStr | Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc. |
| title_full_unstemmed | Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc. |
| title_short | Parameters Influencing Baseline HIV-1 Genotypic Tropism Testing Related to Clinical Outcome in Patients on Maraviroc. |
| title_sort | parameters influencing baseline hiv 1 genotypic tropism testing related to clinical outcome in patients on maraviroc |
| url | https://doi.org/10.1371/journal.pone.0125502 |
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