A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naive Patients Starting a First-Line HAART

作者：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 Genevieve; Calvez Vincent; Antinori Andrea; Ceccherini Silberstein Francesca; Perno Carlo Federico; Santoro Maria Mercedes^*

来源：PLos One, 2014, 9(8): e105853.

DOI：10.1371/journal.pone.0105853

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-naive 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-naive 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.

• 出版日期2014-8-25