The Genotypic False Positive Rate Determined by V3 Population Sequencing Can Predict the Burden of HIV-1 CXCR4-using Species Detected by Pyrosequencing

Valentina Svicher, Valeria Cento, Gabriella Rozera, Isabella Abbate, Maria Mercedes Santoro, Daniele Armenia, Lavinia Fabeni, Alessandro Bruselles, Alessandra Latini, Guido Palamara, Valeria Micheli, Giuliano Rizzardini, Caterina Gori, Federica Forbici, Giuseppe Ippolito, Massimo Andreoni, Andrea Antinori, Francesca Ceccherini-Silberstein, Maria Rosaria Capobianchi, Carlo Federico Perno

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The false-positive rate (FPR) is a percentage-score provided by Geno2Pheno-algorithm indicating the likelihood that a V3-sequence is falsely predicted as CXCR4-using. We evaluated the correlation between FPR obtained by V3 population-sequencing and the burden of CXCR4-using variants detected by V3 ultra-deep sequencing (UDPS) and Enhanced-Sensitivity Trofile assay (ESTA). Methods: 54 HIV-1 B-subtype infected-patients (all maraviroc-naïve), with viremia >10,000copies/ml, were analyzed. HIV-tropism was assessed by V3 population-sequencing, UDPS (considering variants with >0.5% prevalence), and ESTA. Results: By UDPS, CCR5-using variants were detected in 53/54 patients, irrespective of FPR values, and their intra-patient prevalence progressively increased by increasing the FPR obtained by V3 population-sequencing (rho = 0.75, p = 5.0e-8). Conversely, the intra-patient prevalence of CXCR4-using variants in the 54 patients analyzed progressively decreased by increasing the FPR (rho = -0.61; p = 9.3e-6). Indeed, no CXCR4-using variants were detected in 13/13 patients with FPR>60. They were present in 7/18 (38.8%) patients with FPR 20-60 (intra-patient prevalence range: 2.1%-18.4%), in 5/7 (71.4%) with FPR 10-20, in 4/6 (66.7%) with FPR 5-10, and in 10/10(100%) with FPR20 (particularly in the range 20-60), allowing a more careful identification of patients harboring CXCR4-using variants.

Original languageEnglish
Article numbere53603
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 18 2013

ASJC Scopus subject areas

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

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