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

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/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.

Results

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%.

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.

SUBMITTER: Armenia D

PROVIDER: S-EPMC4143365 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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 D Soulie Cathia C Di Carlo Domenico D Fabeni Lavinia L Gori Caterina C Forbici Federica F Svicher Valentina V Bertoli Ada A Sarmati Loredana L Giuliani Massimo M Latini Alessandra A Boumis Evangelo E Zaccarelli Mauro M Bellagamba Rita R Andreoni Massimo M Marcelin Anne-Geneviève AG Calvez Vincent V Antinori Andrea A Ceccherini-Silberstein Francesca F Perno Carlo-Federico CF Santoro Maria Mercedes MM

PloS one 20140825 8

<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 ...[more]

PMID: 25153969

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