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

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 103H/N/S/T 100I • • • 101E/Q 106M 181C 106A • • • 188L 103R und 179D 179E • • • 190A/C/E/Q/S 181I/V • • • 3 aus (98G , 101E/Q, 106A/I, 108I, 230L 190T/V • • 179D/E, 181IV, , 190T/V, 225H, 101P 227L, 234I, 236L, 238T/N, 318F ) 225H • • 230I 234I • • 188CH 236L • • 238T/N • 318F •

NVP HIV-GRADE update Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Resistant Intermediate Resistance Limited Susceptibility 103H/N/S/T 103R und 179D 100I • • • 106A/M 101E/Q • • • 3 aus (98G, 100I, 101E/Q, 106I, 181CVI 190T/V • • 108I, 179D/E, 190T/V, 225H, 227L, 188C/H/L 234I, 236L, 238T/N, 318F) 225H • • 190A/C/E/Q/S 234I • • 230L 236L • • 101P 238T/N • • 318F •

DTG HIV-GRADE update Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Resistent Intermediate Resistance Limited Susceptibility • Q148HKR + 2 out of • Q148HKR + 1 out of • A49G • Q148HKR • T66I (G140ACS, L74IM, (G140ACS, L74IM, • N155H • L74I E138AKT) E138AKT) • S230GR • 148RH + 140S • N155H + 1 out of ( • E92Q • V260I • T97A E92Q, T97A, Y143R, • G118R L74IM, E138AKT) • R263K • E138AKT • G140ACS • Y143R • S147G Dosage adaptions for DTG according to the current version of the label should be considered.

Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin HIV2EU Ruleset

Nucleoside reverse transcriptase Inhibitors Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Substance Resistant Intermediate Resistance AZT •Q151M •S215ACFLY •S215ACFLY + 1 of (N69ST, K70R, Y115F, K223R) •Q151M •S215ACFLY d4T •S215ACFLY + 1 of (K65R, N69ST, •K65R K70R, Y115F, K223R) • not recommended* •M184VI •K65R 3TC/FTC • Q151M •2 of (M184VI, S215ACFLY, D67N, K70RN) ABC • K65R • M184VI+1 of (L74V , Y115F ) TDF/TAF • K65R • Q151M+V111I • K65R ddI • L74V * Not recommended due to rapid • Q151M resistance development •not recommended*

Non-nucleoside reverse transcriptase Inhibitors Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Not effective against HIV-2, not recommended due to natural resistance

Protease Inhibitors Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Substance Resistant Intermediate Resistance SQV •G48V • I84V •L90M LPV •2 of (I82F, I84V, L90M) • V62A+ L99F •I54M • 1 of (I82F, I84V, L90M) •V47A DRV • I50V • 1 of (I84V, L90M) • I54M • I84V + L90M • I50L • I54L ATV • I82F • ATV not recommended • natural resistance TPV •I54M IDV •I82F •I84V •V62A + L99F •L90M •IDV not recommended • natural resistance fAPV

Integrase Inhibitors Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Substance Resistant Intermediate Resistance • N155HR •E92Q RAL • Q148KR •Y143CGR • 1 of (E92Q, T97A) + Y143CGR • E92Q + T97A EVG* • E92QG • Y143C •Q148KR •T97A + Y143C •N155H DTG* •G140S + Q148R •Q148R •Q148K •N155H •E92Q + N155H •E92Q •T97A + N155H •Y143C + T97A *Rules based almost exclusively on in-vitro data

Fusion Inhibitors Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin T-20 not recommended

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

External Quality Assessment Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin I NSTAND e.V.

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) INSTAND IQVD GBD

Evalution of results • Three level approach • Evaluation of sequence quality • Evaluation of resistance associated mutations • Evaluation of resistance interpretation

Genetic distance based calculation of sequence quality INSTAND

Evaluation of mutations

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

Participants Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin Dez 2015/Jan 2016 Nov 2016 Dez 2014/Jan 2015 (383) (384) (383) (384) (383) (384) Standard- Zusat Standard- Zusatzprog. Standard- Zusatzprog. Prog. zprog. Prog. Prog. Participants from 30 24 33 28 34 30 Germany inkl. Pilot inkl. Pilot Participants from 6 2 5 3 6 6 other countries Number of countries 5 3 6 3 6 5

EQA results Success rates Medic ical C l Center er f for Infectio ious s Disea seases ses Berli lin PR/RT INT + V3 YEAR SQ MUT Interp. SQ MUT Interp. 2014-2015 96.3% 96.4% 96.4% 100% 100% 100% 94% 94% 94% 2015-2016 80.6% 72.9% 43.2% 100% 100% 100% 96% 96% 96% INSTAND

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