A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.

<h4>Background</h4>We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immuno...

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Autores principales: Daniele Armenia, Cathia Soulie, Domenico Di Carlo, Lavinia Fabeni, Caterina Gori, Federica Forbici, Valentina Svicher, Ada Bertoli, Loredana Sarmati, Massimo Giuliani, Alessandra Latini, Evangelo Boumis, Mauro Zaccarelli, Rita Bellagamba, Massimo Andreoni, Anne-Geneviève Marcelin, Vincent Calvez, Andrea Antinori, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Maria Mercedes Santoro
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spelling oai:doaj.org-article:7e6433be8198451ca3064997384df80b2021-11-25T06:03:15ZA very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.1932-620310.1371/journal.pone.0105853https://doaj.org/article/7e6433be8198451ca3064997384df80b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25153969/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.<h4>Methods</h4>The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses.<h4>Results</h4>Overall, at therapy start, 27% of patients had FPR ≤ 10 (6%, FPR ≤ 2; 7%, FPR 2-5; 14%, FPR 5-10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%.<h4>Conclusions</h4>Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.Daniele ArmeniaCathia SoulieDomenico Di CarloLavinia FabeniCaterina GoriFederica ForbiciValentina SvicherAda BertoliLoredana SarmatiMassimo GiulianiAlessandra LatiniEvangelo BoumisMauro ZaccarelliRita BellagambaMassimo AndreoniAnne-Geneviève MarcelinVincent CalvezAndrea AntinoriFrancesca Ceccherini-SilbersteinCarlo-Federico PernoMaria Mercedes SantoroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105853 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Daniele Armenia
Cathia Soulie
Domenico Di Carlo
Lavinia Fabeni
Caterina Gori
Federica Forbici
Valentina Svicher
Ada Bertoli
Loredana Sarmati
Massimo Giuliani
Alessandra Latini
Evangelo Boumis
Mauro Zaccarelli
Rita Bellagamba
Massimo Andreoni
Anne-Geneviève Marcelin
Vincent Calvez
Andrea Antinori
Francesca Ceccherini-Silberstein
Carlo-Federico Perno
Maria Mercedes Santoro
A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
description <h4>Background</h4>We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.<h4>Methods</h4>The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses.<h4>Results</h4>Overall, at therapy start, 27% of patients had FPR ≤ 10 (6%, FPR ≤ 2; 7%, FPR 2-5; 14%, FPR 5-10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%.<h4>Conclusions</h4>Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.
format article
author Daniele Armenia
Cathia Soulie
Domenico Di Carlo
Lavinia Fabeni
Caterina Gori
Federica Forbici
Valentina Svicher
Ada Bertoli
Loredana Sarmati
Massimo Giuliani
Alessandra Latini
Evangelo Boumis
Mauro Zaccarelli
Rita Bellagamba
Massimo Andreoni
Anne-Geneviève Marcelin
Vincent Calvez
Andrea Antinori
Francesca Ceccherini-Silberstein
Carlo-Federico Perno
Maria Mercedes Santoro
author_facet Daniele Armenia
Cathia Soulie
Domenico Di Carlo
Lavinia Fabeni
Caterina Gori
Federica Forbici
Valentina Svicher
Ada Bertoli
Loredana Sarmati
Massimo Giuliani
Alessandra Latini
Evangelo Boumis
Mauro Zaccarelli
Rita Bellagamba
Massimo Andreoni
Anne-Geneviève Marcelin
Vincent Calvez
Andrea Antinori
Francesca Ceccherini-Silberstein
Carlo-Federico Perno
Maria Mercedes Santoro
author_sort Daniele Armenia
title A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
title_short A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
title_full A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
title_fullStr A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
title_full_unstemmed A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART.
title_sort very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line haart.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/7e6433be8198451ca3064997384df80b
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