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

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 PernoMaria Mercedes Santoro

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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/mm3) and on the time to achieve virological success (the first HIV-RNA measurement 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%. Conclusions: 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.

Original languageEnglish
Article numbere105853
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 25 2014

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Highly Active Antiretroviral Therapy
immune response
drugs
Pharmaceutical Preparations
Hazards
tropisms
Tropism
RNA
CD4 Lymphocyte Count
Human immunodeficiency virus 1
HIV-1
therapeutics
cells
normal values
HIV
Therapeutics
Population

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART. / Armenia, Daniele; Soulie, Cathia; Di Carlo, Domenico; Fabeni, Lavinia; Gori, Caterina; Forbici, Federica; Svicher, Valentina; Bertoli, Ada; Sarmati, Loredana; Giuliani, Massimo; Latini, Alessandra; Boumis, Evangelo; Zaccarelli, Mauro; Bellagamba, Rita; Andreoni, Massimo; Marcelin, Anne Geneviève; Calvez, Vincent; Antinori, Andrea; Ceccherini-Silberstein, Francesca; Perno, Carlo Federico; Santoro, Maria Mercedes.

In: PLoS One, Vol. 9, No. 8, e105853, 25.08.2014.

Research output: Contribution to journalArticle

Armenia, D, Soulie, C, Di Carlo, D, Fabeni, L, Gori, C, Forbici, F, Svicher, V, Bertoli, A, Sarmati, L, Giuliani, M, Latini, A, Boumis, E, Zaccarelli, M, Bellagamba, R, Andreoni, M, Marcelin, AG, Calvez, V, Antinori, A, Ceccherini-Silberstein, F, Perno, CF & Santoro, MM 2014, 'A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART', PLoS One, vol. 9, no. 8, e105853. https://doi.org/10.1371/journal.pone.0105853
Armenia, Daniele ; Soulie, Cathia ; Di Carlo, Domenico ; Fabeni, Lavinia ; Gori, Caterina ; Forbici, Federica ; Svicher, Valentina ; Bertoli, Ada ; Sarmati, Loredana ; Giuliani, Massimo ; Latini, Alessandra ; Boumis, Evangelo ; Zaccarelli, Mauro ; Bellagamba, Rita ; Andreoni, Massimo ; Marcelin, Anne Geneviève ; Calvez, Vincent ; Antinori, Andrea ; Ceccherini-Silberstein, Francesca ; Perno, Carlo Federico ; Santoro, Maria Mercedes. / A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART. In: PLoS One. 2014 ; Vol. 9, No. 8.
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abstract = "Background: 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. Methods: The analysis was performed on 305 HIV-1 B subtype infected drug-na{\"i}ve 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/mm3) and on the time to achieve virological success (the first HIV-RNA measurement 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{\%}. Conclusions: Beyond the genotypically-inferred tropism determination, FPR ≤2{\%} predicts both a poor immunological reconstitution and a lower virological response in drug-na{\"i}ve 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.",
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T1 - A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART

AU - Armenia, Daniele

AU - Soulie, Cathia

AU - Di Carlo, Domenico

AU - Fabeni, Lavinia

AU - Gori, Caterina

AU - Forbici, Federica

AU - Svicher, Valentina

AU - Bertoli, Ada

AU - Sarmati, Loredana

AU - Giuliani, Massimo

AU - Latini, Alessandra

AU - Boumis, Evangelo

AU - Zaccarelli, Mauro

AU - Bellagamba, Rita

AU - Andreoni, Massimo

AU - Marcelin, Anne Geneviève

AU - Calvez, Vincent

AU - Antinori, Andrea

AU - Ceccherini-Silberstein, Francesca

AU - Perno, Carlo Federico

AU - Santoro, Maria Mercedes

PY - 2014/8/25

Y1 - 2014/8/25

N2 - Background: 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. Methods: 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/mm3) and on the time to achieve virological success (the first HIV-RNA measurement 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%. Conclusions: 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.

AB - Background: 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. Methods: 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/mm3) and on the time to achieve virological success (the first HIV-RNA measurement 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%. Conclusions: 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.

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