Medic ical C l Center er f for Infectio ious s Disea seases - - PowerPoint PPT Presentation

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin RPV HIV-GRADE update Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Resistant Imtermediate resistance Limited susceptibility

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

RPV HIV-GRADE update

Resistant Imtermediate resistance Limited susceptibility

  • Score of 3 and

higher

  • Score of 2
  • Score of 1

3 Points: 101P , 138K, 181IV, 230LI, 138RAGQS + 184I, 100I + 103SN, 100I + 103R + 179D 2 Points: 138RAGQS, 101E, 181C, 188L, 189I 1 Point: 90I, 100I, 221Y , 230V, 179L, 227C

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

DTG HIV-GRADE update

Resistent Intermediäre Resistenz Eingeschränkte Empfindlichkeit

  • Q148HKR + 2 out of

(G140ACS, L74I, E138AKT)

  • 148RH + 140S
  • Q148HKR + 1 out of

(G140ACS, L74I, E138AKT)

  • N155H + 1 out of (

E92Q, T97A, Y143R, L74IM, E138AKT)

  • R263K
  • L74IM
  • E92Q
  • T97A
  • G118R
  • E138AKT
  • Y143R
  • Q148HKR
  • G140ACS
  • N155H
  • V260I
  • S147G

Dosage adaptions for DTG according to the current version of the label should be considered.

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Miscellaneous

  • Renaming:
  • TDF/TAF instead of TDF
  • geno2pheno:
  • Update to new geno2pheno version
  • Connection by REST service
  • Automated update of the cut-offs
  • Interface add on
  • Output of result as JSON or XML
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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Work in progess

  • Easier batch interpretation
  • Output as XLSX-spreadsheet
  • Update of interface
  • Configurable report
  • User specific defaults
  • Speed up of parser
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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

HIV2EU

Ruleset

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Nucleoside reverse transcriptase Inhibitors

Substance Resistant Intermediate Resistance AZT

  • Q151M
  • S215ACFLY + 1 of (N69ST, K70R,

Y115F, K223R)

  • S215ACFLY

d4T

  • Q151M
  • S215ACFLY + 1 of (K65R, N69ST,

K70R, Y115F, K223R)

  • not recommended*
  • S215ACFLY
  • K65R

3TC/FTC

  • M184VI
  • K65R

ABC

  • Q151M
  • K65R
  • M184VI+1 of (L74V , Y115F )
  • 2 of (M184VI, S215ACFLY, D67N, K70RN)

TDF/TAF

  • K65R
  • Q151M+V111I

ddI

  • K65R
  • L74V
  • Q151M
  • not recommended*

* Not recommended due to rapid resistance development

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Non-nucleoside reverse transcriptase Inhibitors

Not effective against HIV-2, not recommended due to natural resistance

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Protease Inhibitors

Substance Resistant Intermediate Resistance SQV

  • G48V
  • L90M
  • I84V

LPV

  • 2 of (I82F, I84V, L90M)
  • I54M
  • V47A
  • V62A+ L99F
  • 1 of (I82F, I84V, L90M)

DRV

  • I50V
  • I54M
  • I84V + L90M
  • 1 of (I84V, L90M)

ATV

  • I50L
  • I82F
  • ATV not recommended
  • I54L

TPV

  • natural resistance

IDV

  • I54M
  • I82F
  • I84V
  • V62A + L99F
  • L90M
  • IDV not recommended

fAPV

  • natural resistance
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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Integrase Inhibitors

Substance Resistant Intermediate Resistance RAL

  • N155HR
  • Q148KR
  • 1 of (E92Q, T97A) + Y143CGR
  • E92Q + T97A
  • E92Q
  • Y143CGR

EVG*

  • E92QG
  • Q148KR
  • T97A + Y143C
  • N155H
  • Y143C

DTG*

  • G140S + Q148R
  • Q148K
  • E92Q + N155H
  • T97A + N155H
  • Q148R
  • N155H
  • E92Q
  • Y143C + T97A

*Rules based almost exclusively on in-vitro data

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Fusion Inhibitors

T-20 not recommended

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Tropism

For tropism determination use: Geno2pheno[coreceptor-HIV2]

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Tropism

Visseaux, Benoit, Margarita Hurtado-Nedelec, Charlotte Charpentier, Gilles Collin, Alexandre Storto, Sophie Matheron, Lucile Larrouy, Florence Damond, Françoise Brun-Vézinet, und Diane Descamps. „Molecular Determinants of HIV-2 R5–X4 Tropism in the V3 Loop: Development of a New Genotypic Tool“. Journal of Infectious Diseases 205, Nr. 1 (1. Januar 2012): 111–20. doi: 10.1093/ infdis/ jir698.

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External Quality Assessment

I NSTAND e.V.

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EQA Results PR/RT

INSTAND e.V.

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EQA results INT

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EQA results Tropism

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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

Thank you

Thomas Berg, Patrick Braun, Martin Däumer, Josef Eberle, Robert Ehret, Rolf Kaiser, Claudia Kücherer, Harm Müller, Christian Noah, Martin Obermeier, Martin Stürmer, Alexander Thielen, Jens Verheyen, Hauke Walter, Eva Wolf Special thanks to Marcel Schütze, Heinz Zeichhardt, Oliver Donoso and Hans-Peter Grunert