Background: Assessment of human immunodeficiency virus type 1 (HIV-1) coreceptor usage is required prior to treatment with the CCR5 antagonist maraviroc to exclude the presence of CXCR4-using (X4) strains. Genotype-based interpretation systems are mostly designed on subtype B and have been reported to be less accurate for subtype A/CRF02_AG. Objectives: To evaluate the performance of the widely used Geno2Pheno[coreceptor] (G2P[c]) algorithm for prediction of coreceptor usage with subtype A/CRF02_AG vs. subtype B. Study design: Co-receptor tropism of 24 subtype A/CRF02_AG and 24 subtype B viruses was measured phenotypically by a homebrew single-cycle assay and genotypically by using G2P[c]. Samples with discrepant genotype-phenotype results were analyzed by next generation sequencing (NGS) and interpreted by the NGS Geno2Pheno algorithm (G2P). Results: At 10% false positive rate (FPR), the G2P[c]/phenotype discordance rate was 12.5% (n = 3) for subtype A/CRF02_AG and 8.3% (n = 2) for subtype B. Minority X4 species escaping detection by bulk sequencing but documented by NGS explained the two subtype B and possibly one subtype A/CRF02_AG discordant case. The other two subtype A/CRF02_AG miscalled by G2P[c] could be explained by X4 overcalling at borderline FPR and/or by algorithm failure. Discussion: Our study did not demonstrate relevantly higher G2P[c] inaccuracy with subtype A/CRF02_AG with respect to subtype B. Genotype/phenotype discordances can be due to different reasons, including but not limited to, algorithm inaccuracy. Very large genotype/phenotype correlation panels are required to detect and explain the reason for any consistent difference in genotypic tropism prediction for subtype A/CRF02_AG vs. subtype B.
Performance of Geno2Pheno[coreceptor] to infer coreceptor use in human immunodeficiency virus type 1 (HIV-1) subtype A / I. Vicenti, A. Lai, A. Giannini, A. Boccuto, F. Dragoni, F. Saladini, M. Zazzi. - In: JOURNAL OF CLINICAL VIROLOGY. - ISSN 1386-6532. - 111(2019 Feb), pp. 12-18.
|Titolo:||Performance of Geno2Pheno[coreceptor] to infer coreceptor use in human immunodeficiency virus type 1 (HIV-1) subtype A|
LAI, ALESSIA (Secondo)
|Parole Chiave:||Coreceptor usage; Genotype; HIV-1 tropism; NGS; Phenotype; Subtype A; Virology; Infectious Diseases|
|Settore Scientifico Disciplinare:||Settore MED/42 - Igiene Generale e Applicata|
Settore MED/07 - Microbiologia e Microbiologia Clinica
|Data di pubblicazione:||feb-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jcv.2018.12.007|
|Appare nelle tipologie:||01 - Articolo su periodico|