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Journal of Clinical Microbiology, February 2007, p. 279-284, Vol. 45, No. 2
0095-1137/07/$08.00+0     doi:10.1128/JCM.01118-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Determining Human Immunodeficiency Virus Coreceptor Use in a Clinical Setting: Degree of Correlation between Two Phenotypic Assays and a Bioinformatic Model

Katharina Skrabal,^1, Andrew J. Low,^2,4, Winnie Dong,² Tobias Sing,³ Peter K. Cheung,^2,4 Fabrizio Mammano,^1,5 and P. Richard Harrigan^2,4*

INSERM U552 Recherche Antivirale, Paris, France,¹ B.C. Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada,² Max-Planck-Institute for Informatics, Saarbrücken, Germany,³ Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada,⁴ Faculté de Médecine, Université Denis Diderot Paris 7, Paris, France⁵

Received 31 May 2006/ Returned for modification 3 August 2006/ Accepted 13 November 2006

Two recombinant phenotypic assays for human immunodeficiency virus (HIV) coreceptor usage and an HIV envelope genotypic predictor were employed on a set of clinically derived HIV type 1 (HIV-1) samples in order to evaluate the concordance between measures. Previously genotyped HIV-1 samples derived from antiretroviral-naïve individuals were tested for coreceptor usage using two independent phenotyping methods. Phenotypes were determined by validated recombinant assays that incorporate either an 2,500-bp ("Trofile" assay) or an 900-bp (TRT assay) fragment of the HIV envelope gp120. Population-based HIV envelope V3 loop sequences (105 bp) were derived by automated sequence analysis. Genotypic coreceptor predictions were performed using a support vector machine model trained on a separate genotype-Trofile phenotype data set. HIV coreceptor usage was obtained from both phenotypic assays for 74 samples, with an overall 85.1% concordance. There was no evidence of a difference in sensitivity between the two phenotypic assays. A bioinformatic algorithm based on a support vector machine using HIV V3 genotype data was able to achieve 86.5% and 79.7% concordance with the Trofile and TRT assays, respectively, approaching the degree of agreement between the two phenotype assays. In most cases, the phenotype assays and the bioinformatic approach gave similar results. However, in cases where there were differences in the tropism results, it was not clear which of the assays was "correct." X4 (CXCR4-using) minority species in clinically derived samples likely complicate the interpretation of both phenotypic and genotypic assessments of HIV tropism.

Published ahead of print on 22 November 2006.

K.S. and A.J.L. contributed equally to this work.

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