Tropism Determination for HIV-1 Subtype C Isolates Alexandra Haas - PowerPoint PPT Presentation

Tropism Determination for HIV-1 Subtype C Isolates Alexandra Haas Joëlle Bader Thomas Klimkait May 9 th 2015 Department of Biomedicine-Haus Petersplatz, Molecular Virology University of Basel

HIV-1 entry and fusion Adapted from Moore et al. (2003) PNAS Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Global distribution of HIV-1 subtypes IAVI Report, August 2003 Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Tropism determination for Subtype CRF01_AE from Asia • Predominant strain in South-East Asia • Geno2Pheno results discordant to phenotypic results • Overcalling of CXCR4-tropic HIV-1 by Geno2Pheno Subtype C? Can a similar discordance be observed for Subtype C? Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Workflow XTrack C Geno2Pheno PhenX-R Capillary-based nucleic Sequence ‐ based Replicative phenotyping acid duplex tracking assay interpretation of amino acid system information Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

XTrack system Klimkait et al. (2014) J. Clin. Microbiol. Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Study Characteristics • HIV-1 subtype C strains from Southern Africa • All show viral loads >1000 copies/mL • All under failing cART • For For XTrack analysis n = 125 patients • For G2P coreceptor analysis n=46 (25 R5 and 21 X4) Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Results X4 R5 undefined mixed XTrack X4 Geno2Pheno R5 X4  Good agreement for 70% of cases R5 Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Outlook • Increase number of Geno2Pheno analyses • Validation of our findings with replicative phenotyping • New generation of V3 primers • Retraining of algorithms? Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Thank you for your attention! Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel