treatment-experienced patients in central and eastern...

Treatment-experienced Patients in Central and Eastern Europe ndash What needs to be done

Aster VDepartment of Infectious and Tropical Diseases Hospital Bulovka Prague

Case study 1)Alexandr 50y MSMbull Dg HIV in 1990 CD4+ 30 (in 1990) 1997 CMV retinitis stage C3bull repeated hospitalisations (repeated respiratory infections diarrhoea

syphilis herpes zoster epididymitis condyloma polyneuropathy cachexia collapses injuries)

ART regimenshelliphelliphelliphelliphelliphellip ART not regularly usedhelliphelliphelliptill 2016 not supressed1992 AZT Sep 1996 AZT+DDC (zalcitabine) NucacutesDec 1996 AZT+ SAQ (saquinavir) (cause of switch dyspepsia) PInoncomplianceNov 1997 SAQ + 3TC + AZT Jun 1999 IDV (indinavir) + D4T (stavudine) + EFV (cause of switch rezistance) PI Jul 1999 ART stopped (dyspepsia)Jan 2002 IDV (indinavir) + D4T (stavudine) + EFV reintroduced PIOct 2006 LPVr +D4T (stavudine) + EFV (cause of switch dyspepsia) PINov 2007 noncomplianceMay 2008 FPV+RTV + FTC+TDF introduced PIMay 2011 noncomplianceJul 2011 EFV +FTC+TDF introduced NucacutesJun 2013 noncomplianceSep 2014 RTG+ ETR INI

Case study 2)

Sep 2016 resistance test for ARV drugs providedComplete resistance NUCacutes ABC AZT D4T ddI EFV NVP RPV Complete resistance INI EVG RTG Partial resistance NUCacutes TDF ETR NO resistance PI fAPV ATV DRV IDV LPV NFV SQV TPVNO resistance NUCacutes 3TC FTCNO resistance INI DTG

Since Oct 2016 (till now) LPVr+DTGhelliphelliphellip helliphellip CD4+ 542 CD4+CD8+ 028 virologically supressed Feb 2018 ETV (introduced because of HBV coinfection and DAA therapy)

March 2016 Acute VHB(even HBV vaccination completed in 2007)

(CD4+ 343)

HBsAg positive till now

HBV viral loadsApr 2016 483 000 000 IUml Aug 2016 1 200 000 000 IUml Nov 2017 205 000 000 IUml

HBV resistance test providedNo resistance to TDF 3TC ETV ADVFeb 2018 therapy by ETV introduced

Mar 2018 2 420 000 IUml Apr 2018 708 000 IUml May 2018 197 000 IUml

May 2018 15 800 IUml

time of acquisition unclear but between 2011 and 2016

(in 2011 anti-HCV negative)

GT 1b F 3-4 116 kPa by Fibroscan (Oct 2017)

HCV viral loads

Apr 1-st 2016 29 500 IUml

Mar 21-st 2017 gt10 000 000 IUml

Oct 11-th 2017 19 800 000 IUml

Apr 24-th 2018 therapy by SOFLDV introduced

May 2-nd 2018 11 IUml W2

May 23-rd 2018 lt15 IUml W4

Jun 19-th 2018 negative W8

Jun 17-th 2018 negative W 1 ETR

Oct 10-th 2018 still no result SVR

Case study 3)

HBV coinfection HCV coinfection

ARV drugs available in the Czech Republic

GENVOYA EVGc+FTCTAF

ODEFSEY RPVFTCTAF

TRIUMEQ DGT3TCABC

EMTRICITABTENOFOV FTCTDF

TENOFOVIR DISOMYL TDF

DESCOVY FTCTAF

TIVICAY DTG

ISENTRESS RTG

TENOFOVIR DISOPTV TDF

KALETRA LPVr

KIVEXA ABC3TC

REZOLSTA DRVc

TENOFOVIR DISOSAN TDF

EVIPLERA RPVFTCTDF

NORVIR RTV

TRUVADA FTCTDF

EPIVIR 3TC

EFAVIRENZ TEVA EFV

PREZISTA DRV

STRIBILD EVGc+FTCTDF

EVOTAZ ATVc

INTELENCE ETR

DARUNAVIR MYLAN DRV

ZIAGEN ABC

CELSENTRI MVC

COMBIVIR ZDV3TC

EDURANT RPV

LAMIVUDINZIDOVUDI ZDV3TC

RETROVIR ZDV

TELZIR FPV

EMTRIVA FTC

FUZEON T20

REYATAZ ATV

STOCRIN EFV

VIRAMUNE NVP

TRIZIVIR ZDV3TCABC

ARV drug use in the Czech Republic according drugs prescribed from January to August 2018

45

55

Percentage of ARV one tablet regimes

1 tabday Other regimes

00

50

100

150

200

250

300

350

400

450

500

93 218 192 490 07

NRTI NNRTI PI INI MVC

Percentage of ARV drug use according to particular drug regimes

Number of patients on indivitual ARV regimens in Prague AIDS Center Bulovka

according to drugs prescribed since January till August 2018

0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug

Number of patients according to individual tablet use

INI60

PI21

Nucacutes19

Percentage of use according to particular antiretroviral regimes in in patients from

AIDS Center Bulovka Prague January till August 2018

ART experienced patients in AIDS Center Prague

ART switch is generaly rarely necessary because of toxicity or viral supression failure

Most common reasons for switch in stabilised patients

lower toxicity

FTCTDF FTCTAF

health-care insurancies rules (HIV resistency testing before initiation of elected ART combinations)

HCV therapy (hep-drug interactions)

ART switch need in ART experienced HIVHCV coinfected patients treated by DAA for VHC in Prague AIDS Center (N=25)

Ptoriginal ARV

regimenARV regimen before

and during DAA therapy DAA regimen recent ARV regimen

1 DRVr+FTCTDF RTG+FTCTDF BOC+PR RTG+FTCTDF

2 LPVr+FTCTDF RTG+FTCTDF SMV+PR DTG+FTCTAF

3 EFV+FTCTDF RTG+FTCTDF SMV+PR RTG+FTCTAF

4 RTG+FTCTDF RTG+FTCTDF SMV+PR RTG+FTCTDF

5 DRVr+FTCTDF RTG+FTCTDF SMV+PR EVGc+FTCTAF



8 ZDV3TC+TDF RTG+FTCTDF SMV+PR RTG+FTCTDF

9 LPVr+FTCTDF RTG+FTCTDF SMV+PR EVGc+FTCTAF

10 DRVr+FTCTDF DTG+FTCTDF GZREBV DTG+FTCTDF

11 LPVr+AZT3TC DTG+3TC+TDF GZREBV DTG+3TC+TDF

12 DRVr+FTCTDF DRVr+FTCTDF SOF+DCV+RBV DRVc+ FTCTAF

13 DRVr+FTCTDF RTG+FTCTDF OBVPTVr+DSV RTG+FTCTAF

14 LPVr+FTCTDF RTG+FTCTDF SOFLDV RTG+FTCTDF

15 LPVr+FTCTDF RTG+FTCTAF SOFLDV RTG+FTCTAF

16 LPVr+RTG RTG+FTCTDF SOFLDV DTG+FTCTAF

17 LPVr+TDF+RTG LPVr+TDF+RTG SOFLDV LPVr+RTG

18 NO NO SOFLDV+RBV EVGc+FTCTAF

19 LPVr+DTG LPVr+DTG SOFLDV LPVr+DTG

20 DRVr+FTCTDF RTG+FTCTDF SOFLDV EVGc+FTCTDF

21 ZDV3TC+TDF RTG+FTCTDF SOFVEL RTG+FTCTAF

22 ETV+FTCTDF DTG+FTCTAF SOFVEL DTG+FTCTAF

23 EFV+3TC+TDF DTG+3TC+TDF SOFVEL DTG+3TC+TDF

24 EFV+FTCTDF DTG+FTCTAF SOFVEL DTG+FTCTAF

25 RTG+FTCTDF RTG+ABC3TC SOFVEL RTG+ABC3TC

18 (72) out of 25 pts switched

DAA before DAA therapy

0

5

10

15

20

25

7

12

6switch fromNUCacutes

switch fromPI

no switch

72

14 56

11

44

no switch switch


ARV after DAA therapy

Case study 1-st rdquoexperienceldquo in DAA therapy

Jaroslava 41 y (at the time of HCV dg in 2006) Family history mother died in 53 y liver cirrhosis father died in 75 y

gastric cancer brother died in 39 y liver cirrhosis Personal history repeated pneumonia in childhood depression

thyreopathy on substitution therapy

Present illness Y 2006 dg VHC not treatet (thyreopathy) July 2009 clinically liver Ci (biopsy not performed) HCV VL 5 410 000

IUml GT 1b started Peg-IFNRBV finished after 5 W because of AE (facial palsy)

November 2009 axillar and cervical lymphadenopathy dg DLBCL lymphoma after 6 R-CHOP series since March 2010 in remission

December 2012 ascites diuretic therapy started (spironolacton) October 2013 lymphoma relapsed started therapy by steroids

rituximab CHT radiotherapy no remission February 2014 worsening of liver functions stage CH-P B (7 points) and

signes of portal hypertension (CHS 51 total protein 597 gl alb 440 INR 11 leu 21 Hb 121 plt 57 USG spleen 15cm portal vein 18mm endoscopy 1-st grade oesophageal varices)

Not included to waiting list for liver transplantation (lymphoma) IFN-free therapy indicated

Case study 1-st bdquoexperienceldquo in DAA therapySofosbuvirledipasvir approved but not covered by health-care insurance companies in the Czech

Republic at the beginning of 2015 but reimbursement was possible on basis of special request

hepatologist request for SOFLDV therapy reimbursement

health-care insurance company answer

1 (January 2015) hellippatient with CHVHC liver cirrhosis 464 kPa asciteshellip

NO bdquolymphoma no data about safety and effectivenes in treatment by Harvoni in hematooncologic patients existldquo

2 (March 2015)hellipldquo15 of pts with NHL are HCV infected SOFLDV has no myelotoxic potency SVR has beneficial effect in pts with lymphomaldquo1)

1) Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B-cell non-Hodgkin lymphomas ANRS HC-13 lympho-C studyMichot JM at all ANRS HC-13 Lympho-C Study GroupAm J Hematol 2015 Mar90(3)197-203 doi 101002ajh23889 Epub 2014 Nov 24

NO bdquosend to us fulltext of the paperldquohellipldquono study with Harvoni nad patients with lymphoma existldquo

3 (April 2014) hellipldquopatient with decompensated lymphoma cannot wait for such studiesldquohellipfull text1) has been sent

NO bdquono studies about safety and effectivenes in patients with lymphomaldquo

July 26-th 2015 patient admitted to ID dept (liver failure) July 30-th 2015 patient died (51 y)

Retreatment after DAAacutes regimen (exept IFN including and SOFRBV regimens)

according the EASL guidelines 2018

European Association for the Study of the Liver EASL Recommendations on Treatment of Hepatitis C 2018 J Hepatol (2018) httpsdoiorg101016j jhep201803026

Pts without Ci or with compensated Ci (whofailed after PI or NS5A regimen)

SOFVELVOX 12W

Pts without Ci or with compensated Ci (whofailed after PI or NS5A regimen) and have predictors of lower response

SOF+GLEPIB 12W

Very difficult to cure pts (with RASs and who failed twice PI and NS5A regimen)

SOFVELVOX + RBV 12-24 WorSOF+GLEPIB + RBV 12-24W

Pts with decompensated Ci who failed after PI andor NS5A

SOFVEL + RBV 24 W

RAS testing recommended Multidisciplinary team decision is recommended

Previously DAA treated patients and RAS testing real problem

Polaris 1 study TE pacients 150 with GT 1 with NS5A experience and 114 pts with other GT SOFVELVOX for 12 W SVR 96 was achieved1)

Substudy Polaris 1 147 NS5A TE patients with GT 1 with NS5A experience who previously received placebo were treated by SOFVELVOX for 12 W 97 SVR was achieved 2)

Polaris 4 study 163 TE pts but not previously treated by NS5A pts with GT 12 or 3 and 19 pts with GT 4 SOFVELVOX for 12 W

SVR 98 was achieved1)

248 NS5A TE patients 205 of them had baseline NS3 andor NS5A RASs were treated by SOFVELVOX for 12 W 97 SVR was achieved No impact of baseline RASs on treatment outcome was confirmed 3)

1) Bourlieacutere M et all bdquoSofosbuvir Velpatasvir and Voxilaprevir for Previously Treated HCV InfectionldquoN Engl J Med 2017 Jun 1376(22)2134-2146 doi 101056NEJMoa1613512

2) Bouliere m et all bdquoDeferred treatment with sofosbuvir-velpatasvir-voxilaprevir for patients with chronic hepatitis Cvirus who were previously treated with an NS5A inhibitor an open-label substudy of POLARIS-1ldquoLancet Gastroenterol Hepatol 2018 Aug3(8)559-565 doi 101016S2468-1253(18)30118-3 Epub 2018 May 313) Sarrazin C et all bdquoNo impact of resistance-associated substitutions on the efficacy of sofosbuvir velpatasvir and voxilaprevir for 12 weeks in HCV DAA-experienced patientsldquo J Hepatol 2018 Aug 9 pii S0168-8278(18)32279-7 doi 101016jjhep201807023 [Epub ahead of print]

When SOFVELVOX and GLEPIB are not available RAS testing might have sense and previous DAA

treatment might be a problem

1) Mawatari S et all The co-existence of NS5A and NS5B resistance-associated substitutions is associated with virologic failure in Hepatitis C Virus genotype 1 patients treated with sofosbuvir and ledipasvir PLoS One 2018 Jun 113(6)e0198642 doi 101371journalpone0198642 eCollection 2018

493 patients with GT 1b were treated by SOFLDV (31 of them had by DCVASV treatment history) The SVR 12 in 966 was achieved 1)

the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (833) 1)

the SVR12 rates in the patients with IFN-free treatment-naive and retreated were 976 and 806 respectively 1)

All DAAacutes available in the Czech Republic

bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB

DAA therapy in the Czech Republic

264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int

Bulovka PraguePardubice

Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM

Centers for DAA therapy Number of treated patients

1) HARM registry HCV Patients treatment Guarantor of the project Prof MUDr P Urbanek CSc Project managert Mgr M Barinova Data analysis Mgr M Kuhn2) Data from IKEM with obliging permisson included

Number of patients treated by DAA in individual centersfor DAA therapy in the Czech Republic

from 1-st Jan 2016 to 26-th Jan 26 1 2018 (n=1052) according tothe HARM registry 1)2)

19 Centers for DAA treatment in the Czech Republic

AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41

Distribution of care for HIV+ patients

in the Czech Republic (Feb 2018)1)

1) Maly M Nemecek V National institute of Health 2016

Prague center in Bulovka Hospital cares about both HCV monoinfected and HCVHIV coinfected patients

There is no experience in treatment in DAA experienced patients because of small cohort of treated patients

resulting from not satisfactory resources Still all our DAA treated patients were succesfully treated

No experience in Prague Center Bulovka in treatment in TE patients

Outlook on situation in HCV treatment by DAA in Prague Center Hospital Bulovka waiting and treated patients

according to the place of treatment and HIV coinfection status No=134

(till 5-th Sep 2018 personal experience)

Other centers specialists obliging to help in access to DAA treatment for patients from Prague Center Hospital Na Bulovce Frankova S Dlouhy P Wolfova M Hejda V Urbanek P

0

5

10

15

20

25

30

35

40

45

HIVHCV HCV HIVHCV HCV HIVHCV HCV

Treated in Bulovka Treated in other center waiting

1622

4

30

21

41patients


Treatment experienced and Treatment naive Patients treated by DAA in the Czech Republic

from January 1-st 2016 to January 26-th (n=1052)Data from 18 centers elected for DAA treatment1)2)

TE 488

46

TN 564

54

Treatment experienced and Treatment naive Patients (n=1052)

TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3

Treatment experienced and Treatment naive Patients according the

Genotypes (n=1052)

Treatment experienced Patients with known previous regimen treated by DAA (n=385)

in the Czech Republic since January 1-st 2016 till January 26-th 2018

Data from 18 centers elected for DAA treatment 1)2)

Previous regimen GT 1(n=369)

GT 3(n=16)

DACLATASVIR + ASUNAPREVIR 2 (05 )

DASABUVIR + OMBITASVIR + PARITAPREVIRRITONAVIR 1 (03 )

PEG-IFN + RBV 270 (732 ) 15 (938 )

PEG-IFN + RBV + BOCEPREVIR 52 (141 )

PEG-IFN + RBV + SIMEPREVIR 15 (41 )

PEG-IFN + RBV + SOFOSBUVIR 2 (05 )

PEG-IFN + RBV + TELAPREVIR 14 (38 )

SOFOSBUVIR + DACLATASVIR 1 (03 )

SOFOSBUVIR + DACLATASVIR + RBV 1 (63 )

SOFOSBUVIRLEDIPASVIR 1 (03 )

Other 11 (30 )

1) HARM registry HCV Patients treatmentGuarantor of the project Prof MUDr Petr Urbanek CScProject managert Mgr Magda BarinovaData analysis Mgr Matyas Kuhn2) Data from IKEM with obliging permisson included

Only 6 (16) out of 386 treatment

experienced patients were treated after INF-free regimen failure

DAA treatment failure in 19 patients from IKEM(Data from Institute of Clinical and Experimental

Medicine (IKEM) Prague) Frankova Sona MD PhD

Pt GT Failure Fibrosis CPs Comorbidities reason Retreatment Result

10 1b DACASU F4 A NO advanced cirrhosis although CPA still not NA



13 1b SOFLDV F4 A NO PPI RBV not used Y93H L31F SOFSIM SVR

18 1b SOFLDV F4 B NO PPI still not NA

19 1b SOFLDV F4 NA OLTx rituximab early after Tx L31M L28N 3D SVR

1 1a SOFLDV FCH after OLTx NA OLTx unquantifiable high viraemia SOFVELVOX NA

5 1b SOFLDV F4 B NO comedication PPI still not NA

7 1b SOFLDV F4 A NO PPI SOFVELVOX NA

9 1b SOFLDV FCH after OLTx NA OLTx PPI still not NA

15 1b 3D F4 A NO susp noncompliance still not NA

16 1b 3D FCH after OLTx NA OLTx D168V L28T restist to OMB SOFLDV SVR

17 1b 3D F4 A NO advanced cirhosis although CPA Y93H SOFVELVOX NA

2 1b 3D F2 NA NO hepatotoxicity stopping th at W5 SOFVELVOX NA

3 1b 3D F1 NA NO H93Y SOFVELVOX NA

6 1b 3D F4 A TIPS noncompliance no (HCC) NA

8 1b 3D F1 NA NO SOFVELVOX NA

14 3a SOFDAC F4 A renal failure advanced cirrhosis although CPA SOFVELVOX NA

4 1b GZREBV F4 A NO still not NA

Expert answersIn order of problem graveness total CZ SK SK UA SLO TR RUS PL RO H BY LT

coverage of out of label regimens 26 2 2 3 2 1 3 1 3 3 3 2 1

drug price 25 32 3 1 2 1 3 1 1 2 3

3

missing of new drugs on the market 25 1 2 2 3 1 3 3 1 3 2 2 2

selftherapy by unregistered drugs 24 21 1 3 1 3 2 2 3 2 2

2

RAS testing availability 21 13 2 3 1 2 1 2 1 2 2

1

delay in processing of endorsement 21 21 2 3 1 3 1 2 2 2

2

delay in processing of coverage 21 21 2 3 1 1 2 1 2 2 2

2

local guidelines 17 1 2 2 2 1 1 2 1 1 1 1 2

high percentage of treatment failure 13 1

1 1 1 1 1 1 1 2 1 11

Problems in DAA therapy in CEE countries results from questionare given to colleagues from other CEE countries

Answers from 13 experts from 12 CEE countries were received Grade of problem (from 1 to 3) 1=no problem 2=possibly problematic 3=serious problem

Conclusions Switch of ART regimen is common in

ART treatment experienced patients before starting HCV therapy

Redistribution of sources for DAA therapy in the Czech Republic has to be provided

46 of DAA therapies in treatment experienced patients is provided in the Czech Republic

DAA price is not the contemporary leading problem in CEE countries

Continuation in communication between experts in HIVhepatitis coinfections across CEE counties is needed

Acknowledgement

All colleageous from AIDS Center Bulovka Hospital Prague Ladislav Machala David Jilich Dan Vesely Lukas Fleishans

IKEM Prague Sona Frankova

HARM MUHP Prague Petr Urbanek

All colleagous from CEE countries Pavol Kristian (Slovakia) Pavol Jarcuska (Slovakia) Svitlana Antonyak (Ukraine) Mojca Maticic (Slovenia) Pavel Khaykin (Germany) Cihan Yurdaydin (Turkey) Vadim Rassokhin Vadim (Russian Federation) Agata Skrzat-Klapaczyńska (Poland) Anca Streinu-Cercel (Romania) Botond Lakatos (Hungary) Nalia Matievskaja (Belarus) Raimonda Matulionyte (Lithuania)

Case study 1)Alexandr 50y MSMbull Dg HIV in 1990 CD4+ 30 (in 1990) 1997 CMV retinitis stage C3bull repeated hospitalisations (repeated respiratory infections diarrhoea

syphilis herpes zoster epididymitis condyloma polyneuropathy cachexia collapses injuries)

ART regimenshelliphelliphelliphelliphelliphellip ART not regularly usedhelliphelliphelliptill 2016 not supressed1992 AZT Sep 1996 AZT+DDC (zalcitabine) NucacutesDec 1996 AZT+ SAQ (saquinavir) (cause of switch dyspepsia) PInoncomplianceNov 1997 SAQ + 3TC + AZT Jun 1999 IDV (indinavir) + D4T (stavudine) + EFV (cause of switch rezistance) PI Jul 1999 ART stopped (dyspepsia)Jan 2002 IDV (indinavir) + D4T (stavudine) + EFV reintroduced PIOct 2006 LPVr +D4T (stavudine) + EFV (cause of switch dyspepsia) PINov 2007 noncomplianceMay 2008 FPV+RTV + FTC+TDF introduced PIMay 2011 noncomplianceJul 2011 EFV +FTC+TDF introduced NucacutesJun 2013 noncomplianceSep 2014 RTG+ ETR INI

Case study 2)




(CD4+ 343)





May 2018 15 800 IUml




HCV viral loads

Apr 1-st 2016 29 500 IUml

Mar 21-st 2017 gt10 000 000 IUml

Oct 11-th 2017 19 800 000 IUml







Case study 3)



GENVOYA EVGc+FTCTAF

ODEFSEY RPVFTCTAF

TRIUMEQ DGT3TCABC



DESCOVY FTCTAF

TIVICAY DTG

ISENTRESS RTG


KALETRA LPVr

KIVEXA ABC3TC

REZOLSTA DRVc


EVIPLERA RPVFTCTDF

NORVIR RTV

TRUVADA FTCTDF

EPIVIR 3TC

EFAVIRENZ TEVA EFV

PREZISTA DRV


EVOTAZ ATVc

INTELENCE ETR

DARUNAVIR MYLAN DRV

ZIAGEN ABC

CELSENTRI MVC

COMBIVIR ZDV3TC

EDURANT RPV


RETROVIR ZDV

TELZIR FPV

EMTRIVA FTC

FUZEON T20

REYATAZ ATV

STOCRIN EFV

VIRAMUNE NVP

TRIZIVIR ZDV3TCABC


45

55



00

50

100

150

200

250

300

350

400

450

500

93 218 192 490 07





0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug


INI60

PI21

Nucacutes19






lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement





Case study 2)




(CD4+ 343)





May 2018 15 800 IUml




HCV viral loads

Apr 1-st 2016 29 500 IUml

Mar 21-st 2017 gt10 000 000 IUml

Oct 11-th 2017 19 800 000 IUml







Case study 3)



GENVOYA EVGc+FTCTAF

ODEFSEY RPVFTCTAF

TRIUMEQ DGT3TCABC



DESCOVY FTCTAF

TIVICAY DTG

ISENTRESS RTG


KALETRA LPVr

KIVEXA ABC3TC

REZOLSTA DRVc


EVIPLERA RPVFTCTDF

NORVIR RTV

TRUVADA FTCTDF

EPIVIR 3TC

EFAVIRENZ TEVA EFV

PREZISTA DRV


EVOTAZ ATVc

INTELENCE ETR

DARUNAVIR MYLAN DRV

ZIAGEN ABC

CELSENTRI MVC

COMBIVIR ZDV3TC

EDURANT RPV


RETROVIR ZDV

TELZIR FPV

EMTRIVA FTC

FUZEON T20

REYATAZ ATV

STOCRIN EFV

VIRAMUNE NVP

TRIZIVIR ZDV3TCABC


45

55



00

50

100

150

200

250

300

350

400

450

500

93 218 192 490 07





0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug


INI60

PI21

Nucacutes19






lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement






(CD4+ 343)





May 2018 15 800 IUml




HCV viral loads

Apr 1-st 2016 29 500 IUml

Mar 21-st 2017 gt10 000 000 IUml

Oct 11-th 2017 19 800 000 IUml







Case study 3)



GENVOYA EVGc+FTCTAF

ODEFSEY RPVFTCTAF

TRIUMEQ DGT3TCABC



DESCOVY FTCTAF

TIVICAY DTG

ISENTRESS RTG


KALETRA LPVr

KIVEXA ABC3TC

REZOLSTA DRVc


EVIPLERA RPVFTCTDF

NORVIR RTV

TRUVADA FTCTDF

EPIVIR 3TC

EFAVIRENZ TEVA EFV

PREZISTA DRV


EVOTAZ ATVc

INTELENCE ETR

DARUNAVIR MYLAN DRV

ZIAGEN ABC

CELSENTRI MVC

COMBIVIR ZDV3TC

EDURANT RPV


RETROVIR ZDV

TELZIR FPV

EMTRIVA FTC

FUZEON T20

REYATAZ ATV

STOCRIN EFV

VIRAMUNE NVP

TRIZIVIR ZDV3TCABC


45

55



00

50

100

150

200

250

300

350

400

450

500

93 218 192 490 07





0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug


INI60

PI21

Nucacutes19






lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement






GENVOYA EVGc+FTCTAF

ODEFSEY RPVFTCTAF

TRIUMEQ DGT3TCABC



DESCOVY FTCTAF

TIVICAY DTG

ISENTRESS RTG


KALETRA LPVr

KIVEXA ABC3TC

REZOLSTA DRVc


EVIPLERA RPVFTCTDF

NORVIR RTV

TRUVADA FTCTDF

EPIVIR 3TC

EFAVIRENZ TEVA EFV

PREZISTA DRV


EVOTAZ ATVc

INTELENCE ETR

DARUNAVIR MYLAN DRV

ZIAGEN ABC

CELSENTRI MVC

COMBIVIR ZDV3TC

EDURANT RPV


RETROVIR ZDV

TELZIR FPV

EMTRIVA FTC

FUZEON T20

REYATAZ ATV

STOCRIN EFV

VIRAMUNE NVP

TRIZIVIR ZDV3TCABC


45

55



00

50

100

150

200

250

300

350

400

450

500

93 218 192 490 07





0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug


INI60

PI21

Nucacutes19






lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement






45

55



00

50

100

150

200

250

300

350

400

450

500

93 218 192 490 07





0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug


INI60

PI21

Nucacutes19






lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement







0 100 200 300 400

383

245

245

238

236

167

150

136

129

101

64

21

ATVc

DRV

DRVc

RPVFTCTDF

LPVr

RPVFTCTAF

DTGTAFABC

RTG

FTCTAF

DTG

EVGcFTCTAF

FTCTDF

No of patientsDrug


INI60

PI21

Nucacutes19






lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement








lower toxicity

FTCTDF FTCTAF




Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement






Ptoriginal ARV






























0

5

10

15

20

25

7

12


switch fromPI

no switch

72

14 56

11

44

no switch switch






























SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement
































SOFVELVOX 12W


SOF+GLEPIB 12W




SOFVEL + RBV 24 W

















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement




















bull RBV

bull DAC

bull SOF

bull SOFLDV

bull SOFVEL

bull SOFVELVOX

bull GZREBV

bull OBVPRVr+DSV

bull GLEPIB


264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement






264

127

106

97

79

74

48

44

37

35 (33)30

30

23

23

16

7

0 50 100 150 200 250 300

Remedis Prague

Hradec K int

Hradec K inf

VFN Prague

Opava

Olomouc

Motol Prague int


Motol Prague inf

C Budejovice

Transplant surg

Ostrava

UVN Prague

Plzen

Brno

IKEM






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement






AIDS Center

Bulovka 1639

59

Other AIDS

Centers1153 41












0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement









0

5

10

15

20

25

30

35

40

45



1622

4

30

21

41patients




TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement








TE 488

46

TN 564

54


TE 469TE 19

TN 510TN 54

0

10

20

30

40

50

60

70

80

90

100

GT 1 GT 3


Genotypes (n=1052)





GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement









GT 3(n=16)



PEG-IFN + RBV 270 (732 ) 15 (938 )








Other 11 (30 )




























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement





























drug price 25 32 3 1 2 1 3 1 1 2 3

3



2


1


2


2



1 1 1 1 1 1 1 2 1 11









Acknowledgement











Acknowledgement





treatment-experienced patients in central and eastern...

Documents