Performance Evaluation of a Genotypic Tropism Test Using HIV-1 CRF01_AE Isolates in Japan

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  • Matsuda Masakazu
    Department of Infectious Diseases and Immunology, National Hospital Organization Nagoya Medical Center
  • Louvel Séverine
    InPheno AG
  • Sugiura Wataru
    Department of Infectious Diseases and Immunology, National Hospital Organization Nagoya Medical Center
  • Haas Alexandra
    Molecular Virology, Department Biomedicine — Petersplatz, University of Basel
  • Pfeifer Nico
    Max Planck Institute for Informatics, Computational Biology and Applied Algorithmics
  • Yokomaku Yoshiyuki
    Department of Infectious Diseases and Immunology, National Hospital Organization Nagoya Medical Center
  • Iwatani Yasumasa
    Department of Infectious Diseases and Immunology, National Hospital Organization Nagoya Medical Center
  • Kaiser Rolf
    Institute of Virology, University of Cologne
  • Klimkait Thomas
    Molecular Virology, Department Biomedicine — Petersplatz, University of Basel

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<p>Geno2Pheno (coreceptor), a genotypic tropism test, demonstrates excellent agreement with the phenotypic tropism test for subtype B and some other subtypes. However, potential X4-overcalling for CRF01_AE might occur with the present version. To confirm X4 overcalling for AE and to optimize the algorithm for use with AE, we compared the tropism of 22 AE samples by both genotypic and phenotypic methods. The env V3 region was analyzed by bulk sequencing, and tropism was evaluated using the Geno2Pheno algorithm. PhenXR, a phenotypic tropism test, was performed in parallel to determine chemokine receptor preferences. A high X4-overcalling for select samples and a low rate of R5-concordant samples (9.1%) were observed for AE with the current version of Geno2Pheno (coreceptor). On the other hand, the new version, namely, Geno2Pheno (Sanger), showed a high concordance rate of 81.8%, with PhenXR. Because majority of the samples were selected based on discrepancies in the genotypic tropism calls between the present version Geno2Pheno (coreceptor) (FPR<10%) and the new version Geno2Pheno (Sanger) (X4-risk<36), it remains to be determined whether the new version provides improved R5-calls for the AE sequences in general or only in this setting. Further clinical validation studies are warranted.</p>

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