Performance of commonly used genotypic assays and comparison with phenotypic assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients.
J Antimicrob Chemother
; 70(5): 1391-5, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25608585
ABSTRACT
OBJECTIVES:
Although founder viruses in primary HIV-1 infections (PHIs) typically use the CCR5 coreceptor (R5-tropic), 3%-19% of subjects also harbour CXCR4-using viruses (X4-tropic), making tropism determination before CCR5 antagonist usage mandatory. Genotypic methods can be used to accurately determine HIV-1 tropism in chronically infected patients.METHODS:
We compared the results of genotypic methods [geno2pheno, PSSMx4r5 including a novel nucleotide-input version (ntPSSM) and distant segments (ds)Kernel] to predict coreceptor usage in a cohort of 67 PHIs. Specimens with discrepant results were phenotypically tested after cloning the V3 gene region into proviral backbones. Recombinant viruses were used to infect U87 indicator cell lines bearing CD4 and either CCR5 or CXCR4.RESULTS:
Geno2pheno10%, PSSMx4r5 and (ds)Kernel gave identical predictions in 85% of cases. Geno2pheno10% predicted the presence of CXCR4 viruses in 18% of patients. Two patients were predicted to carry X4-tropic viruses by all algorithms and X4-tropic viruses were detected in at least one of the recombinant AD8 or NL4-3 backbone-based assays. Ten samples resulted in discordant predictions with at least one algorithm. Full concordance between tropism prediction by using population sequencing and phenotypic assays was observed only with ntPSSM. Geno2pheno prediction and the phenotypic assay gave the same results in a minority of 'discordant' patients.CONCLUSIONS:
Compared with both PSSMx4r5 versions, (ds)Kernel and our phenotypic assay, geno2pheno10% overestimated the frequency of X4-tropic viruses (18% versus 3%). ntPSSM was able to detect one additional X4 virus compared with (ds)Kernel that was confirmed with the phenotypic assay.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cultivo de Virus
/
Infecciones por VIH
/
Receptores del VIH
/
VIH-1
/
Tropismo Viral
/
Técnicas de Genotipaje
Tipo de estudio:
Evaluation_studies
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia