The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing.
<h4>Objective</h4>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-u...
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2013
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oai:doaj.org-article:7be4060c35a74e85964f9b67de9f8f002021-11-18T08:01:39ZThe genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing.1932-620310.1371/journal.pone.0053603https://doaj.org/article/7be4060c35a74e85964f9b67de9f8f002013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341955/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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 FPR<5 (intra-patient prevalence range: 12.1%-98.1%).<h4>Conclusions</h4>FPR by V3 population-sequencing can predict the burden of CXCR4-using variants. This information can be used to optimize the management of tropism determination in clinical practice. Due to its low cost and short turnaround time, V3 population-sequencing may represent the most feasible test for HIV-1 tropism determination. More sensitive methodologies (as UDPS) might be useful when V3 population-sequencing provides a FPR >20 (particularly in the range 20-60), allowing a more careful identification of patients harboring CXCR4-using variants.Valentina SvicherValeria CentoGabriella RozeraIsabella AbbateMaria Mercedes SantoroDaniele ArmeniaLavinia FabeniAlessandro BrusellesAlessandra LatiniGuido PalamaraValeria MicheliGiuliano RizzardiniCaterina GoriFederica ForbiciGiuseppe IppolitoMassimo AndreoniAndrea AntinoriFrancesca Ceccherini-SilbersteinMaria Rosaria CapobianchiCarlo Federico PernoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53603 (2013) |
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Medicine R Science Q |
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Medicine R Science Q 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 The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing. |
| description |
<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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 FPR<5 (intra-patient prevalence range: 12.1%-98.1%).<h4>Conclusions</h4>FPR by V3 population-sequencing can predict the burden of CXCR4-using variants. This information can be used to optimize the management of tropism determination in clinical practice. Due to its low cost and short turnaround time, V3 population-sequencing may represent the most feasible test for HIV-1 tropism determination. More sensitive methodologies (as UDPS) might be useful when V3 population-sequencing provides a FPR >20 (particularly in the range 20-60), allowing a more careful identification of patients harboring CXCR4-using variants. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Valentina Svicher |
| title |
The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing. |
| title_short |
The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing. |
| title_full |
The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing. |
| title_fullStr |
The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing. |
| title_full_unstemmed |
The genotypic false positive rate determined by V3 population sequencing can predict the burden of HIV-1 CXCR4-using species detected by pyrosequencing. |
| title_sort |
genotypic false positive rate determined by v3 population sequencing can predict the burden of hiv-1 cxcr4-using species detected by pyrosequencing. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/7be4060c35a74e85964f9b67de9f8f00 |
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