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

tropism determination for hiv 1 subtype c isolates
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Tropism Determination for HIV-1 Subtype C Isolates Alexandra Haas - - PowerPoint PPT Presentation

Tropism Determination for HIV-1 Subtype C Isolates Alexandra Haas Jolle 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.


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SLIDE 1

Tropism Determination for HIV-1 Subtype C Isolates

May 9th 2015 Department of Biomedicine-Haus Petersplatz, Molecular Virology University of Basel

Alexandra Haas Joëlle Bader Thomas Klimkait

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SLIDE 2

Adapted from Moore et al. (2003) PNAS

HIV-1 entry and fusion

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

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SLIDE 3

Global distribution of HIV-1 subtypes

IAVI Report, August 2003

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

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SLIDE 4

Tropism determination for Subtype CRF01_AE from Asia

  • Predominant strain in South-East Asia

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Subtype C? Can a similar discordance be

  • bserved for Subtype C?
  • Geno2Pheno results discordant to phenotypic results
  • Overcalling of CXCR4-tropic HIV-1 by Geno2Pheno
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SLIDE 5

XTrackC Capillary-based nucleic acid duplex tracking assay Geno2Pheno Sequence‐based interpretation of amino acid information PhenX-R Replicative phenotyping system

Workflow

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

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SLIDE 6

XTrack system

Klimkait et al. (2014) J. Clin. Microbiol.

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

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SLIDE 7
  • 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)

Study Characteristics

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

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SLIDE 8

Results

X4 R5 XTrack

undefined mixed

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel

Geno2Pheno

X4

R5

X4

R5

 Good agreement for 70% of cases

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SLIDE 9

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

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SLIDE 10

Thank you for your attention!

Department of Biomedicine-Haus Petersplatz, Molecular Virology, University of Basel