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Performance of Geno2Pheno[coreceptor] to infer coreceptor use in human immunodeficiency virus type 1 (HIV-1) subtype A.
Vicenti, Ilaria; Lai, Alessia; Giannini, Alessia; Boccuto, Adele; Dragoni, Filippo; Saladini, Francesco; Zazzi, Maurizio.
Afiliación
  • Vicenti I; Department of Medical Biotechnologies, University of Siena, Siena, Italy. Electronic address: ilariavicenti@gmail.com.
  • Lai A; Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
  • Giannini A; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Boccuto A; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Dragoni F; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Saladini F; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Zazzi M; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
J Clin Virol ; 111: 12-18, 2019 02.
Article en En | MEDLINE | ID: mdl-30594700
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[454]). 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Algoritmos / Receptores del VIH / VIH-1 / Tropismo Viral Tipo de estudio: Evaluation_studies Límite: Humans Idioma: En Revista: J Clin Virol Asunto de la revista: VIROLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Algoritmos / Receptores del VIH / VIH-1 / Tropismo Viral Tipo de estudio: Evaluation_studies Límite: Humans Idioma: En Revista: J Clin Virol Asunto de la revista: VIROLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Países Bajos