PLoS ONE (Jan 2014)

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 Perno,
  • Maria Mercedes Santoro

DOI
https://doi.org/10.1371/journal.pone.0105853
Journal volume & issue
Vol. 9, no. 8
p. e105853

Abstract

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BackgroundWe 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.MethodsThe 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 ResultsOverall, 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%.ConclusionsBeyond 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.