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


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


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


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


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


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)


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


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


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


Telaprevir

Genotype 1B

Results (6) Factors associated with VR24

Boceprevir

Naïve Non responders

Relapsers

Genotype 1A

Cirrhotic Non- cirrhotic

Genotype 1B


Relapsers

Genotype 1A


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


Results (7) Virological response in cirrhotic non responders


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


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


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 (-)


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


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.


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.


Back-up slides


Telaprevir

Genotype 1B

Boceprevir


Relapsers

Genotype 1A


Genotype 1B


Relapsers

Genotype 1A


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


Virological response

W4 W12 W24 W48 W4 W12 W24 W48


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%


Telaprevir

Genotype 1B

Boceprevir


Relapsers

Genotype 1A


Genotype 1B


Relapsers

Genotype 1A


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

background - objectives

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