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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin EFV HIV-GRADE update Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Resistant Intermediate 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

EFV HIV-GRADE update

Resistant Intermediate Resistance Limited Susceptibility

  • 103H/N/S/T
  • 106M
  • 188L
  • 190A/C/E/Q/S
  • 230L
  • 101P
  • 100I
  • 181C
  • 103R und 179D
  • 3 aus (98G , 101E/Q, 106A/I, 108I,

179D/E, 181IV, , 190T/V, 225H, 227L, 234I, 236L, 238T/N, 318F )

  • 230I
  • 188CH
  • 101E/Q
  • 106A
  • 179E
  • 181I/V
  • 190T/V
  • 225H
  • 234I
  • 236L
  • 238T/N
  • 318F
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Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin

NVP HIV-GRADE update

Resistant Intermediate Resistance Limited Susceptibility

  • 103H/N/S/T
  • 106A/M
  • 181CVI
  • 188C/H/L
  • 190A/C/E/Q/S
  • 230L
  • 101P
  • 103R und 179D
  • 3 aus (98G, 100I, 101E/Q, 106I,

108I, 179D/E, 190T/V, 225H, 227L, 234I, 236L, 238T/N, 318F)

  • 100I
  • 101E/Q
  • 190T/V
  • 225H
  • 234I
  • 236L
  • 238T/N
  • 318F
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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 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
  • G140ACS
  • Y143R
  • S147G
  • Q148HKR
  • N155H
  • S230GR
  • V260I

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

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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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

External Quality Assessment

I NSTAND e.V.

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INSTAND IQVD GBD

INSTAND EQASs Nov/Dec 2016 – Groups 383 & 384 HIV-1 Drug Resistance Determination

Organization and EQA-advisory

Institut für Qualitätssicherung in der Virusdiagnostik - IQVD der GBD mbH, Berlin (1) INSTAND e.V. - Gesellschaft zur Förderung der Qualitätssicherung in Medizinischen Laboratorien e.V., Düsseldorf (2) GBD Gesellschaft für Biotechnologische Diagnostik mbH, Berlin (3)

Heinz Zeichhardt (1) (2), Martin Kammel (1) (2), Vanessa Lindig (1), Christiane Meyer-Weydig (1), Hans-Peter Grunert (3)

Scientific cooperation partners (4) and Expert laboratories (5)

Nationales Referenzzentrum für Retroviren (until Sep 2016), Universitätsklinikum Frankfurt, Institut für Medizinische Virologie

  • V. Kempf / H. F. Rabenau / A. Berger / M. Stürmer* (4) (5)

*IMD Medizinisches Versorgungszentrum, Frankfurt (since Feb 2017)

  • Nationales Referenzzentrum für Retroviren (since Oct 2016), Ludwig-Maximilians-Universität München, Max-von-Pettenkofer Inst., Klin. Virologie
  • O. T. Keppler / J. Eberle / L. Gürtler (4) (5)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Institut für Klinische und Molekulare Virologie
  • K. Überla / K. Korn (4) (5)
  • MIB Medizinisches Infektiologiezentrum Berlin
  • M. Obermeier / M. Schütze (4) (5)
  • Uniklinik Köln, Institut für Virologie, Nationales Referenzzentrum für Papillom- und Polyomaviren
  • H. Pfister / R. Kaiser / E. Heger (4) (5)
  • U. Wieland / S. Silling
  • Universität Leipzig, Institut für Virologie

U.G. Liebert / M. Maier (5)

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Evalution of results

  • Three level approach
  • Evaluation of sequence quality
  • Evaluation of resistance associated mutations
  • Evaluation of resistance interpretation
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Genetic distance based calculation of sequence quality INSTAND

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Evaluation of mutations

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

Evaluation of Interpretation

INSTAND

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

Participants

Dez 2014/Jan 2015 Dez 2015/Jan 2016 Nov 2016 (383) Standard- Prog. (384) Zusat zprog. (383) Standard- Prog. (384) Zusatzprog. (383) Standard- Prog. (384) Zusatzprog. Participants from Germany 30

  • inkl. Pilot

24 inkl. Pilot 33 28 34 30 Participants from

  • ther countries

6 2 5 3 6 6 Number of countries 5 3 6 3 6 5

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

EQA results Success rates

PR/RT INT + V3 YEAR SQ MUT Interp. SQ MUT Interp. 2014-2015 96.3% 96.4% 96.4% 100% 94% 100% 94% 100% 94% 2015-2016 80.6% 72.9% 43.2% 100% 96% 100% 96% 100% 96%

INSTAND

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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