HIV RESISTENCE/ HIV TROPISM AREV I R 2 0 1 8 S TA D T H OT E L A - PowerPoint PPT Presentation

HIV RESISTENCE/ HIV TROPISM AREV I R 2 0 1 8 S TA D T H OT E L A M RÖ M E RT U R M , K Ö L N 0 4 . – 0 5 . M A I 2 0 1 8 Dr. Stefan Scholten In den RingColonnaden

F I NANCI AL DI SCL OSURE Abbott/abbvie, BMS, Gilead, GSK, Hexal, Hormonsan, Janssen-Cilag, MSD, TAD, ViiV Healthcare

Three cases: One of those patients … (an update and new development) - It‘s never as easy as one thinks! - Always ask twice! -

Three cases: One of those patients … (an update and new development) - It‘s never as easy as one thinks! - Always ask twice! -

44 years, male, MSM Ethnicity: caucasian (spanish) Date of HIV infection: unknown Date of HIV Diagnosis: 1991 CDC-Classification: C 3

Prior medical conditions: Pneumocystis jiruvecii Pneumonia Candida-oesophagitis CMV – infection caMRSA „USA 300“

ART UNTIL 2007 – THE VL WAS NEVER FULLY SUPPRESSED! Diarrhea !!! Nausea and abdominal pain ISR under the use of T-20 Lipodystrophy Pillburden „Drug-Holidays“

GT resistance test 07/2007 Tropism (Trophile): Dual/Mixed INI: Y143R FI: n.d. NRTI: M41L E44D D67N T69D V75M V118I M184V L210W T215Y NNRTI: K101E G190S PI: L10I V32I L33F M46I I47V F53L I54M Q58E N83D L90M ART in ETR EAP: KVX + LPV/r + SQV + ETR + T20 ART commenced 01.08.2012 in DTG CUP: KVX + LPV/r + SQV + ETR + MRV + DTG (2x50mg) Since then he contracted his first syphillis, 3 months later an acute Hepatitis C (GT1a) Then it became clear that he was frequently slamming Crystal Meth He developed a major depression and borderline personality disorder (ongoing)

HCV-RNA und HCV Therapie 1.000.000 100.000.000 LDV/SOF 10.000.000 100.000 HIV RNA [Kopien/ml] 1.000.000 HCV RNA [IU/ml] 10.000 100.000 Fibroscan 2013: 8,4 kPa 1.000 10.000 Fibroscan 19.01.2015: 14,4 kPa 1.000 100 < 40 100 < 40 n.d. 10 < 12 10 SVR 1 1 Okt 12 Dez 10 Dez 11 Apr 12 Sep 12 Feb 13 04.02.2015 19.02.2015 03.03.2015 Apr 15 Jun 11 Aug 12 Nov 12 Mai 13 Nov 13 Mai 14 Nov 14 3TC 1-0-0 3TC -“- ABC ABC 1-0-1 ETR ETR 2-0-2 LPV LPV 2-0-2 SQV SQV T20 T20 MVC 1-0-1 MVC DTG 1-0-1 DTG 39602

2018 LTFU since 03/17 - Last ART prescription 03/17 Showed up again on 23.02.18 Reports having taken at least ONE (blistered) DOSE (morning or evening) once in a while – estimated every third day HIV RNA (23.02.) <40 cps/ml (!) ART simplification appears to be a paramount necessity - options?

RESISTANCE TESTS 2007 / 2012 PRESENT ART: 3TC/ABC+ETR+LPV/R+SQV+DTG+MVC 2007 2012 2007 2012 ≠F53L ≠F53L ≠F53L NRTI PI ≠F53L ≠F53L ≠F53L ≠F53L 2012 2007 2007 2012 +L100I NNRTI +L100I +L100I +L74M, T97A +L100I INI INI naiv +L74M, T97A 2007 2012 +L74M, T97A, Y134R FI +V38A FI - naiv CCR5 FPR 7,4% (fraglich R5-trop) L45M

HCV-PCR remains negative and HIV PCR remains <40 cps/ml Patient reports of increasing inability to adhere, asks if „less“ is possible? … is Fostemsavir (ViiV attachement inhibitor expected in 2018) an option? Could this ART be an Option: DTG bd + MRV bd + Fostemsavir (dose?) ? … what is to do, if he is not coping until 2018 12 (AGAIN a single named patient use)????

WHAT are our options now ??? Option 1: Leave everything as it is … (he is taking only half his ART every third day !!!!) Option 2: D/C/F/TAF + DTG/RPV + MRV 300 qd ????? Option 3: DTG + MK1439( Doravirine )+ MRV +/- Ibalizumab (Trogarzo) iv. every 2 weeks ??? (Trogarzo = 118.000,- $ / year) Option 4: X + fosTemsavir ??? (is to be given TWICE DAILY!!!) ??? Option 5: 13 X + TPV/r ?????????????? (twice daily, diarrhea, pillburden, side effects)

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Three cases: One of those patients … (an update and new developement) - It‘s never as as easy as one thinks! - Allways ask twice ! -

MSM, German, 62 years of age, Retired federal law enforcement officer, diplomatic corps HIV diagnosis 1996 CDC stage C3 First ART 1997

DIAGNOSES

ART HISTORY First ART: 03/97 d4T, ddI, NFV 09/2001 University Hospital Bonn HIV PCR: >100.000 cps/ml CD4: <200µl Diag: Cryptosporidiosis, Syphilis Resistance test: multiple NUC and PI Mutations New ART 10/2001: ABC, 3TC, TDF, EFV, LPV/r Soon after that -> LTFU due to transfer abroad Reappeared in my practice in Cologne 2010

RESISTANCE TEST 2010 HIV VL 7868/ml; CD4: 186/µl (14,3%) Truvada Intelence Prezista/r (b.i.d.) Isentress Tropismus: X4-trop (1,7% FPR)

HIV RNA HCV RNA CD4 10.000.000 2.000 1.800 1.000.000 1.600 HIV RNA [Kopien/ml] acute HCV GT 4 100.000 moderately raised transaminases 1.400 Albumin normal Thrombocytes normal 1.200 10.000 1.000 1.000 CD4 [Zellen/µl] 800 67 600 100 64 <40 (n.d.) 400 10 200 9,8% 1 0 0 0 1 1 2 2 2 2 3 3 4 5 5 6 6 0 1 1 1 2 2 3 3 4 4 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 g l z n g l l l g t z b i p z b p v z b i v b t b v u u u u k a a k e e r o e o o u e e u e u e e u e e O J M J O J J M M D D N D N N A F F J F A F F A S S TDF FTC ETR DRV/r (bid) RAL

Therapieverlauf 44088 HIV RNA HCV RNA CD4 10.000.000 2.000 1.800 1.000.000 1.600 HIV RNA [Kopien/ml] 100.000 1.400 12 weeks IFN+RBV 1.200 10.000 stop due to non response 1.000 & major depression 1.000 CD4 [Zellen/µl] 800 67 600 100 64 21,8% <40 (n.d.) 400 10 200 9,8% 1 0 0 0 1 1 2 2 2 2 3 3 4 5 5 6 6 0 1 1 1 2 2 3 3 4 4 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 g l z n g l l l g t z b i p z b p v z b i v b t b v u u u u k a a k e e r o e o o u e e u e u e e u e e O J M J O J J M M D D N D N N A F F J F A F F A S S TDF FTC ETR DRV/r (bid) RAL

RESISTANCE TEST 2015 (PROVIRAL DNA) 11/2015 FTC TDF ETR DRV DTG RAL Tropismus (08/10): X4-trop (1,7% FPR) = ART Auswahl

Therapieverlauf 44088 HIV RNA HCV RNA CD4 10.000.000 2.000 1.800 1.000.000 1.600 HIV RNA [Kopien/ml] HCV Gt 4 100.000 Tranaminases ↑ 1.400 Albumin → 12 weeks IFN+RBV Thrombocyts → 1.200 10.000 Fibroscan 6,6 kPa stop due to non response 1.000 & major depression 1.000 CD4 [Zellen/µl] 800 22,5% 67 600 100 64 <40 (n.d.) 400 10 200 9,8% 1 0 0 0 1 1 2 2 2 2 3 3 4 5 5 6 6 0 1 1 1 2 2 3 3 4 4 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 g l z n g l l l g t z b i p z b p v z b i v b t b v u u u u k a a k e e r o e o o u e e u e u e e u e e O J M J O J J M M D D N D N N A F F J F A F F A S S TAF TDF TDF FTC FTC ETR DRV/r (bid) DRV/c RAL DTG

Welche HCV Therapie? (2016/2017) HCV Gt 4 / Transaminases ↑ / Albumin → / Thrombocyts → Fibroscan 6,6 kPa HIV therapy: TAF/FTC, DRV/r (q.d.), DTG *(TDF) • Maviret (2017): Combination with DRV/r not recommended

LTFU from 03/2017 until 02/2018 !!! Therapieverlauf 44088 HIV RNA HCV RNA CD4 10.000.000 2.000 1.800 1.000.000 313.000 cps/ml 1.600 HIV RNA [Kopien/ml] 119/µl (10,1%) 100.000 1.400 1.200 10.000 1.000 12 weeks IFN+RBV 1.000 CD4 [Zellen/µl] stop due to non response 800 & major depression 22,5% 600 100 67 64 400 <40 (n.d.) 10 200 1 0 9,8% 0 0 1 1 2 2 2 2 3 3 4 5 5 6 6 7 0 1 1 1 2 2 3 3 4 4 5 8 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 g l z n g l l l g z t z b i p z b p v z b i v b t b v u u u u k a a k e e r o e o o r 2 u u u u e e e e e e e O J M J O J J M M M D D N D N N . A F F J F A F F A S S 2 0 . 3 2 TDF TAF TDF FTC FTC ETR DRV/r (bid) DRV/c RAL DTG

RESISTENCE TEST 201816.02.18

ULTRA DEEP SEQ 16.02.18 Restart ART, need for simplification, what to do?

NEW ART … … AND FUTURE OPTION 13.03.2018 restarted ART ( my decision ): D/C/F/TAF 1 – 0 – 0 DTG 1 – 0 – 1 ! DRV 600 0 – 0 – 1 Cobi 150 0 – 0 – 1 Future Option: Simplification to D/C/F/TAF + DTG qd (as soon as the VL is undetectable) CHC treatment postponed until patient is stable again! 29

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WHAT HAPPEND NEXT? Week 2: HIV VL 1820 CD4 298µl (10,1%) Week 4 (30.04.2018): no show !!!!!!!!!!!!!! YESTERDAY he turned up – „missed a couple of doses…“ Future developement and lab are pending … 32

Three cases: One of those patients … (an update and new development) - It‘s never as as easy as one thinks! - Always ask twice! -

MSM, German, 49 years of age, HIV diagnosis 1994, CDC stage B2 (Herpes Zoster) First ART 2007 Co-Diagnoses: Bronchial Asthma, Hypertension, Lactose intolerance 2011 first presentation at Praxis Hohenstaufenring

HIV PCR undedetable since 11/2010 CD4 (01/2018) 669/µl (28,1%) 35