HIV-GRADE update Arevir Meeting 2018 Eva Heger Matthias Dring - - PowerPoint PPT Presentation

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HIV-GRADE update Arevir Meeting 2018 Eva Heger Matthias Dring - - PowerPoint PPT Presentation

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Med edical Cen enter er for Infec ectious Disea eases es Ber erlin HIV-GRADE update Arevir Meeting 2018 Eva Heger Matthias Dring Martin Obermeier University of Cologne Max Planck Institute for Informatics MIB Berlin 5/2018 Med

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SLIDE 1

Med edical C Cen enter er for

  • r Inf

nfectious us Disease ses Berlin lin

Matthias Döring Max Planck Institute for Informatics Med edical Cen enter er for Infec ectious Disea eases es Ber erlin 5/2018

HIV-GRADE update

Arevir Meeting 2018

Martin Obermeier MIB Berlin Eva Heger University of Cologne

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SLIDE 2

Med edical C Cen enter er for

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nfectious us Disease ses Berlin lin

Updates in progress

  • Major changes are coming to HIV-GRADE
  • Change in structure of interpretation
  • Update of interface
  • Integration of APOBEC mutation data
  • NGS data analysis

5/2018

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SLIDE 3

Med edical C Cen enter er for

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Switching from 4 categories to 3 categories

  • HIV-GRADE interpretation is currently using four different categories
  • Susceptible
  • Limited susceptibility
  • Intermediate Resistance
  • Resistance
  • Category Limited susceptibility will be removed as overinterpretation of

this category often has occurred ,leaving categories

  • Susceptible
  • Intermediate Resistance
  • Resistance
  • Mark-up of specific mutations

5/2018

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SLIDE 4

Med edical C Cen enter er for

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Example DTG

5/2018

Resistent Intermediate Resistance Limited Susceptibility

  • Q148HKR + 2 out of (G140ACS,

L74IM, E138AKT)

  • 148RH + 140S
  • Q148HKR + 1 out of (G140ACS, L74IM,

E138AKT)

  • N155H + 1 out of ( E92Q, T97A,

Y143R, L74IM, E138AKT)

  • R263K
  • A49G
  • T66I
  • L74I
  • E92Q
  • T97A
  • G118R
  • E138AKT
  • Q148HKR
  • N155H
  • S230GR
  • V260I
  • G140ACS
  • Y143R
  • S147G

Resistent Intermediate Resistance Marked up mutations

  • Q148HKR + 1 aus

(G140ACS, L74IM, E138AKT, N155H)

  • N155H + E92Q
  • R263K
  • Q148HKR
  • G140ACS
  • N155H
  • G118R
  • S230R
  • E138K
  • E92Q
  • L74I
  • E138AT
  • V260I
  • T97A
  • Y143R
  • S147G
  • S230G
  • T66I
  • 157Q

OLD NEW

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SLIDE 5

Med edical C Cen enter er for

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nfectious us Disease ses Berlin lin

Example DTG

5/2018

Resistent Intermediate Resistance Marked up mutations

  • Q148HKR + 1 aus

(G140ACS, L74IM, E138AKT, N155H)

  • N155H + E92Q
  • R263K
  • Q148HKR
  • G140ACS
  • N155H
  • G118R
  • S230R
  • E138K
  • E92Q
  • L74I
  • E138AT
  • V260I
  • T97A
  • Y143R
  • S147G
  • S230G
  • T66I
  • 157Q

Resistent Intermediate Resistance Marked up mutations

  • Q148HKR + 2 aus

(G140ACS, L74IM, E138AKT, N155H)

  • Q148HKR + 1 aus

(G140ACS, L74IM, E138AKT, N155H)

  • N155H + E92Q
  • R263K
  • Q148HKR
  • G140ACS
  • N155H
  • G118R
  • S230R
  • E138K

DTG qd DTG bid

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SLIDE 6

Med edical C Cen enter er for

  • r Inf

nfectious us Disease ses Berlin lin

Update of interface

5/2018

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SLIDE 7

Med edical C Cen enter er for

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nfectious us Disease ses Berlin lin

Integration of APOBEC mutations

5/2018

TARGET TARGET-POS REF-AA APO-AA APO-CODON SUBTYPES RT 178 M I ATA

43_02G;10_CD;04_cpx;D;G;02_AG;06_cpx;21 _A2D;34_01B;15_01B;38_BF1;33_01B;32_06 A1;01_AE

RT 179 E K AAA

38_BF1

RT 182 R Q CAA

16_A2D

RT 184 M I ATA

16_A2D;11_cpx;47_BF;20_BG;37_cpx;36_cpx; 18_cpx;01_AE;46_BF;12_BF;10_CD;31_BC;25 _cpx;09_cpx;06_cpx;22_01A1;19_cpx;21_A2D ;A1;35_AD;07_BC;A2;15_01B;42_BF;40_BF;2 9_BF;02_AG;32_06A1;13_cpx;C;B;D;G;F1;34_ 01B;26_AU;38_BF1;33_01B;27_cpx;F2;08_BC ;04_cpx;28_BF;44_BF;43_02G;17_BF;03_AB; 23_BG;14_BG;45_cpx;24_BG;49_cpx;05_DF

RT 185 D N AAT

16_A2D;11_cpx;47_BF;20_BG;37_cpx;36_cpx; 18_cpx;01_AE;46_BF;12_BF;10_CD;31_BC;25 _cpx;09_cpx;06_cpx;22_01A1;19_cpx;21_A2D ;A1;35_AD;07_BC;A2;15_01B;42_BF;40_BF;2 9_BF;02_AG;32_06A1;13_cpx;C;B;D;G;F1;34_ 01B;26_AU;38_BF1;33_01B;27_cpx;F2;08_BC ;04_cpx;28_BF;44_BF;43_02G;17_BF;03_AB; 23_BG;14_BG;45_cpx;24_BG;49_cpx;39_BF;0 5_DF

RT 186 D N AAT

16_A2D;11_cpx;47_BF;20_BG;17_BF;36_cpx; 21_A2D;29_BF;46_BF;12_BF;10_CD;31_BC;2 5_cpx;09_cpx;06_cpx;19_cpx;18_cpx;07_BC;4 2_BF;40_BF;02_AG;32_06A1;B;D;G;43_02G;3 4_01B;38_BF1;F1;F2;04_cpx;28_BF;03_AB;23 _BG;14_BG;45_cpx;24_BG;49_cpx;39_BF;05_ DF

RT 186 D N AAC

13_cpx;27_cpx;C;08_BC;26_AU;44_BF;11_cp x;25_cpx;45_cpx;22_01A1;17_BF;A1;35_AD;3 7_cpx;A2;46_BF;15_01B;38_BF1;33_01B;01_ AE

RT 190 G R AGG

13_cpx;F1;F2;46_BF;04_cpx;49_cpx;11_cpx;0 9_cpx;06_cpx;22_01A1;18_cpx;45_cpx;40_BF; 05_DF

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SLIDE 8

Med edical C Cen enter er for

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nfectious us Disease ses Berlin lin

NGS

  • Participation in the standardization approach of
  • Direct interpretation of this data format in the HIV-GRADE tool
  • Close cooperation with

5/2018

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SLIDE 9

Med edical C Cen enter er for

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Acknowledgements

5/2018