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www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 20 Access to HCV triple therapy with Telaprevir or Boceprevir in a real-life setting in HIV-HCV co-infected patients ANRS CO13 Hepavih Cohort Poizot-Martin I., Gilbert C., Carrieri P., Miailhes P., Billaud E., Dominguez S., Dabis F., Sogni P., Loko M.-A., Salmon D* . for the ANRS CO13 Hepavih group

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Access to HCV triple therapy with Telaprevir or Boceprevir in a real-life setting in HIV-HCV co-infected patients ANRS CO13 Hepavih Cohort. - PowerPoint PPT Presentation

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Page 1: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Access to HCV triple therapy with Telaprevir or Boceprevir in a real-life

setting in HIV-HCV co-infected patientsANRS CO13 Hepavih Cohort

Poizot-Martin I., Gilbert C., Carrieri P., Miailhes P., Billaud E., Dominguez S., Dabis F., Sogni P., Loko M.-A., Salmon D*.

for the ANRS CO13 Hepavih group

Page 2: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Background - Objectives

• First generation anti-HCV protease inhibitors (PI) available in France since 2011

• Triple therapy with these PI leads to a 30% increase of virological response compared to that of standard PegIFN + Ribavirin

• Our aim was to describe access to triple therapy and early results in a « real-life » prospective cohort of HIV-HCV co-infected patients

Page 3: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Methods (1)

• ANRS CO13 Hepavih Cohort: • French prospective multicenter cohort

• 24 clinical centers

• 1324 HIV-HCV co-infected patients

• Population selection for analysis: • Positive HCV-RNA

• HCV genotype 1

• With at least one follow-up visit since January 2011

Page 4: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Methods (2)

• Two groups of eligible patients were compared:

– One who initiated triple therapy

– And one who did not

• Virological response and tolerance to anti-HCV treatment were also evaluated

• Patients who stopped their treatment prematurely without virological data for the next visits were classified as virological failures

Page 5: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Methods (3)

• Rapid virological response (RVR4):

– Undetectable (<15 UI/mL) HCV-RNA at week 4 after initiation*

• Early virological response:

- EVR12: Undetectable HCV-RNA at week 12*

• Severe anemia: - Hb <9 g/dL or a 4.5 g/dL decrease

* of triple therapy

Page 6: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (1)

ANRS CO13 Hepavih cohort1st June 2013 database

N=1324

Eligible patients for analysisN=320

Initiation of a triple therapyN=114 (36%)

No triple therapyN=206 (64%)

Telaprevir n=81Boceprevir n=24Another molecule n=9Outside clinical trials n=80(Telaprevir n=67, Boceprevir n=13)

Page 7: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Page 8: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (3) Potential contra-indications to anti-HCV triple therapy

* Naïve or non responders to previous HCV treatment

§ Only few patients with available data

Initiation of anti-HCV triple

therapy

No anti-HCV triple therapy *

n (%) n (%) p

Psychiatric disorders 27 (23.7) 54 (26.2)

Current active drug use § 1 (2.9) 15 (9.2)

Alcohol > 5 units / day § 0 (0) 9 (5.3)

Non compatible HAART treatment 2 (1.8) 9 (4.6)

Cardiovascular disease 3 (2.6) 9 (4.4)

Decompensated cirrhosis or HCC 4 (3.5) 7 (3.4)

Platelets < 50 000/mm3 3 (2.7) 3 (1.5)

Renal insufficiency 3 (2.6) 5 (2.4)

Anemia (Hb <10 g/dL) 2 (1.8) 1 (0.5)

At least one contra-indication to triple therapy 39 (34.2) 86 (41.7) 0.191

Page 9: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (4)

The 80 patients who initiated triple therapy outside clinical trials were evaluated for efficacy and safety>

100% received HAART with as 3rd agent:

Raltegravir: 43Atazanavir: 22Darunavir: 2Saquinavir: 2

Lopinavir :2Efavirenz: 7

Rilpivirine: 2

Page 10: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

W4 W12 W24 W4 W12 W24

Telaprevir Boceprevir

020

4060

8010

0

2/10 6/10 6/10

20%

60% 60%

020

4060

8010

0

41/59 40/50 28/38

69%80% 74%

Results (5) Virological response

Page 11: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Telaprevir

Genotype 1B

Results (6) Factors associated with VR24

Boceprevir

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

Genotype 1B

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

020

4060

8010

0

82%

9/11

68%

15/22

80%

4/5

020

4060

8010

0

67%

8/12

77%

20/26

020

4060

8010

0

69%

18/26

90%

9/10

020

4060

8010

0

63%

5/8

50%

1/2

020

4060

8010

0

50%

2/4

67%

4/6

020

4060

8010

0

0/0

60%

6/10 0/0

Page 12: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (7) Virological response in cirrhotic non responders

Telaprevir Boceprevir

020

4060

8010

0

0/4 2/4 2/4

50% 50%

W4 W12 W24

020

4060

8010

0

12/20 10/15 6/10

60%67%

60%

W4 W12 W24

Page 13: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (8) Virological response according to HAART

020

4060

8010

0

64%

18/28

73%

8/11

60%

3/5

100%

4/4

Raltegravir Atazanavir Efavirenz Others*

* Others = Darunavir, Saquinavir, Rilpivirine, Lopinavir

VR24

Page 14: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (9) Adverse events during the first 12 weeks

Results are expressed as N (%) or median [IQR]

9 patients had a blood transfusion and 3 received EPO.

Telaprevirn=51

Boceprevirn=10

Anemia < 9 g/dl 18 (35%) 2 (20%)Rash 8 (16%) 0 (0%)Creatinine increase (µmol/L) +7 [-2,+10] +9 [+1,+33]Pneumopathy 1 (2%) 0 (-)Anal pruritus 4 (8%) 0 (-)

Page 15: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Results (10) : Treatment interruptions

20/80 (25%) stopped their treatment prematurely

Median [IQR] treatment duration before stop: 4.6 months [2.7-6.25]

Reasons of treatment stop:

Telaprevir (n=15) Boceprevir (n=5)

Virological failure 10 (66.7%) 4 (80%)

Lung nodule 1 (6.7%) 0 (-)

Mood disorders 0 (-) 1 (6.7%)

Rash* 1 (6.7%) 0 (-)

Severe anemia 2 (13.3%) 0 (-)

Drug toxicity 1 (6.7%) 0 (-)

* Level 1

Page 16: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Conclusion Triple therapy was started despite potential contra-indications to

treatment, mainly psychiatric disorders, present in 34% of treated patients. On the contrary, non treated patients did not have contra indications in 58% of the cases.

• Patients who initiated triple therapy with anti HCV PI were more often cirrhotic, and previously non responders to previous anti-HCV treatment, than patients who remained non treated.

• The rate of virological responses at W24 was high (74% for telaprevir and 60% for boceprevir), with a trend for a better VR in G1b and non cirrhotic patients.

• One must be cautious until assessment of sustained virological response as relapses can occur during the last months or after 48 weeks.

Page 17: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Acknowledgments Patients of the HEPAVIH CohortScientific Committee of the ANRS CO13 HEPAVIH Study Group: D Salmon (principal investigator), F Dabis (principal investigator), M Winnock, MA Loko, P Sogni, Y Benhamou, P Trimoulet, J Izopet, V Paradis, B Spire, P Carrieri, C Katlama, G Pialoux, MA Valantin, P Bonnard, I Poizot-Martin, B Marchou, E Rosenthal, D Garipuy, O Bouchaud, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, C Duvivier, D Vittecoq, D Neau, P Morlat, F BaniSadr, L Meyer, F Boufassa, S Dominguez, B Autran, AM Roque, C Solas, H Fontaine, L Serfaty, G Chêne, D Costagliola, D Zucman, A Simon, E Billaud, P Miailhes, J Polo Devoto, L. Piroth, S Couffin-Cadiergues (ANRS). Clinical Centres (ward / participating physicians): CHU Cochin, Paris (Médecine Interne et Maladies Infectieuses / D Salmon, H Mehawej; Hépato-gastro-entérologie / P Sogni; Anatomo-pathologie / B Terris, Z Makhlouf, G Dubost, F Tessier, L Gibault, F Beuvon, E Chambon, T Lazure; Virologie / A Krivine); CHU Pitié-Salpétrière, Paris (Maladies Infectieuses et Tropicales / C Katlama, MA Valantin, H Stitou; Hépato-gastro-entérologie / Y Benhamou; Anatomo-pathologie / F Charlotte; Virologie / S Fourati); CHU Pitié-Salpétrière, Paris (Médecine Interne / A Simon, P Cacoub, S Nafissa; Anatomo-pathologie / F Charlotte; Virologie / S Fourati), CHU Sainte-Marguerite, Marseille (Service d'Immuno-Hématologie Clinique - CISIH/ I Poizot-Martin, O Zaegel; P Geneau, Virologie / C Tamalet); CHU Tenon, Paris (Maladies Infectieuses et Tropicales / G Pialoux, P Bonnard, F Bani-Sadr, L Slama, T Lyavanc; Anatomo-pathologie / P Callard, F Bendjaballah; Virologie / C Le-Pendeven); CHU Purpan, Toulouse (Maladies Infectieuses et Tropicales / B Marchou ; Hépato-gastro-entérologie / L Alric, K Barange, S Metivier; A Fooladi, Anatomo-pathologie / J Selves; Virologie / F Nicot); CHU Archet, Nice (Médecine Interne / E Rosenthal ; Infectiologie / J Durant; Anatomo-pathologie / J Haudebourg, MC Saint-Paul) ; CHU Avicenne, Bobigny (Médecine Interne – Unité VIH / O Bouchaud; Anatomo-pathologie / M Ziol; Virologie / Y Baazia); Hôpital Joseph-Ducuing, Toulouse (Médecine Interne / M Uzan, A Bicart-See, D Garipuy, MJ Ferro-Collados; Anatomo-pathologie / J Selves; Virologie / F Nicot); CHU Bichat – Claude-Bernard, Paris (Maladies Infectieuses / Y Yazdanpanah, A Gervais; Anatomo-pathologie / H Adle-Biassette); CHU Saint-Louis, Paris (Maladies infectieuses / JM Molina, C Lascoux Combe; Anatomo-pathologie / P Bertheau, J Duclos; Virologie / P Palmer); CHU Saint Antoine (Maladies Infectieuses et Tropicales / PM Girard, K Lacombe, P Campa; Anatomo-pathologie / D Wendum, P Cervera, J Adam; Virologie / N Harchi); CHU Bicêtre, Paris (Médecine Interne / JF Delfraissy, C Goujard, Y Quertainmont; Virologie / C Pallier); CHU Paul-Brousse, Paris (Maladies Infectieuses / D Vittecoq); CHU Necker, Paris (Maladies Infectieuses et Tropicales / O Lortholary, C Duvivier, M Shoai-Tehrani), CHU Pellegrin, Bordeaux (des Maladies Infectieuses et Tropicales / D Neau, A Ochoa, E Blanchard, S Castet-Lafarie, C Cazanave, D Malvy, M Dupon, H Dutronc, F Dauchy, L Lacaze-Buzy; Anatomo-pathologie / P Bioulac-Sage; Virologie / P Trimoulet, S Reigadas), Hôpital Saint-André, Bordeaux (Médecine Interne et Maladies Infectieuses / P Morlat, D Lacoste, F Bonnet, N Bernard, M Bonarek Hessamfar, J Roger-Schmeltz, P Gellie, P Thibaut, F Paccalin, C Martell, M Carmen Pertusa, M Vandenhende, P Mercier, D Malvy, T Pistone, M Catherine Receveur, S Caldato; Anatomo-pathologie / P Bioulac-Sage; Virologie / P Trimoulet, S Reigadas); Hôpital du Haut-Levêque, Bordeaux (Médecine Interne / JL Pellegrin, JF Viallard, E Lazzaro, C Greib; Anatomo-pathologie / P Bioulac-Sage; Virologie / P Trimoulet, S Reigadas), Hôpital FOCH, Suresnes (Médecine Interne / D Zucman, C Majerholc ; Virologie / F Guitard), CHU Antoine Béclère, Clamart (Médecine Interne / F Boue, J Polo Devoto, I Kansau, V Chambrin, C Pignon, L Berroukeche, R Fior, V Martinez; Virologie / C Deback), CHU Henri Mondor, Créteil (Immunologie Clinique / Y Lévy, S Dominguez, JD Lelièvre, AS Lascaux, G Melica), CHU Hôtel Dieu, Nantes (Maladies Infectieuses et Tropicales / F Raffi, E Billaud, C Alavena; Virologie / A Rodallec), Hôpital de la Croix Rousse, Lyon (Maladies Infectieuses et Tropicales/D Peyramond, C Chidiac, P Miailhes, F Ader, F Biron, A Boibieux, L Cotte, T Ferry, T Perpoint, J Koffi, F Zoulim, F Bailly, P Lack, M Maynard, S Radenne, M Amiri; Virologie / Le-Thi Than-Thuy); CHU Dijon, Dijon (Département d'infectiologie / P Chavanet, L Piroth, M Duong Van Huyen, M Buisson, A Waldner Combernoux, S Mahy, R Binois, A Laure Simonet Lann, D Croisier-Bertin) Data collection, management and statistical analyses: D Beniken, AS Ritleng, M Azar, P Honoré, S Breau, A Joulie, M Mole, C Bolliot, F Touam, F André, H. Roukas, C Partouche, G Alexandre, A. Mélard, , J. Baume, , H Hue, D Brosseau, C Brochier, V Thoirain, M Rannou, D Bornarel, S Gohier, C. Chesnel, S Gillet, J Delaune, C Gilbert, L Dequae-Merchadou, A Frosch, J Cohen, G Maradan, C Taieb, F Marcellin, M Mora, C Protopopescu, C Lions, MA Loko, M Winnock.

Page 18: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Back-up slides

Page 19: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Telaprevir

Genotype 1B

Boceprevir

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

Genotype 1B

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

HCV-RNA undetectable at W4 and W12

020

4060

8010

0

17%1/6 0/2

020

4060

8010

0

0/4

25%

1/4

020

4060

8010

0

0/013%1/8 0/0

020

4060

8010

0

67%

8/12

52%

15/29

100%

5/5

020

4060

8010

0

47%

8/17

69%

20/29

020

4060

8010

0

63%

20/32

64%

7/11

Page 20: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Virological response

W4 W12 W24 W48 W4 W12 W24 W48

Telaprevir Boceprevir

020

4060

8010

0

41/59 40/50 28/38 12/27

69%80% 74%

44%

020

4060

8010

0

2/10 6/10 6/10 3/9

20%

60% 60%

33%

Page 21: Background - Objectives

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Telaprevir

Genotype 1B

Boceprevir

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

Genotype 1B

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

HCV-RNA undetectable at W120

2040

6080

100

79%

27/34

92%

12/13

020

4060

8010

0

72%

13/18

84%

27/32

020

4060

8010

0

85%

11/13

74%

23/31

100%

6/6

020

4060

8010

0

63%

5/8

50%

1/2

020

4060

8010

0

50%

2/4

67%

4/6

020

4060

8010

0

0/0

60%

6/10 0/0