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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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
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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
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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
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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
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (1)
ANRS CO13 Hepavih cohort
1st June 2013 database
N=1324
Eligible patients for analysis
N=320
Initiation of a triple therapy
N=114 (36%)
No triple therapy
N=206 (64%)
Telaprevir n=81
Boceprevir n=24
Another molecule n=9
Outside clinical trials n=80
(Telaprevir n=67, Boceprevir n=13)
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (3) Potential contra-indications to anti-HCV triple therapy
Initiation of antiHCV triple
therapy
No anti-HCV triple
therapy *
n (%)
n (%)
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)
39 (34.2)
86 (41.7)
Psychiatric disorders
At least one contra-indication to triple therapy
p
0.191
* Naïve or non responders to previous HCV treatment
§ Only few patients with available data
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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: 43
Atazanavir: 22
Darunavir: 2
Saquinavir: 2
Lopinavir :2
Efavirenz: 7
Rilpivirine: 2
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (5) Virological response
80
80%
60
40
20
60
20
40
69%
74%
80
100
Boceprevir
100
Telaprevir
28/38
W4
W12
W24
60%
2/10
6/10
6/10
W4
W12
W24
20%
0
40/50
0
41/59
60%
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (6) Factors associated with VR24
100
Boceprevir
82%
80%
80
80
100
Telaprevir
60
40
Non
Relapsers
responders
100
80
100
60
60
Noncirrhotic
20
20
Cirrhotic
5/8
0
20/26
0
8/12
50%
40
50%
40
60
40
20
40
Genotype Genotype
1A
1B
67%
63%
1/2
Genotype Genotype
1A
1B
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2/4
4/6
Cirrhotic
Noncirrhotic
0
77%
0/0
Non
Relapsers
responders
Naïve
67%
9/10
6/10
0
0/0
80
69%
20
0
4/5
80
90%
60
80
100
Naïve
15/22
100
0
9/11
18/26
60%
20
20
40
60
68%
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (7) Virological response in cirrhotic non responders
80
60
60%
50%
50%
0/4
2/4
2/4
W4
W12
W24
20
20
40
60%
67%
40
60
80
100
Boceprevir
100
Telaprevir
6/10
W4
W12
W24
0
10/15
0
12/20
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (8) Virological response according to HAART
VR24
64%
73%
* Others =
Darunavir,
Saquinavir,
Rilpivirine,
Lopinavir
60%
20
40
60
80
100
100%
8/11
3/5
4/4
0
18/28
Raltegravir Atazanavir Efavirenz
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Others*
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Results (9) Adverse events during the first 12 weeks
Telaprevir
n=51
Boceprevir
n=10
18 (35%)
2 (20%)
8 (16%)
0 (0%)
+7 [-2,+10]
+9 [+1,+33]
Pneumopathy
1 (2%)
0 (-)
Anal pruritus
4 (8%)
0 (-)
Anemia < 9 g/dl
Rash
Creatinine increase (µmol/L)
Results are expressed as N (%) or median [IQR]
9 patients had a blood transfusion and 3 received EPO.
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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)
10 (66.7%)
4 (80%)
1 (6.7%)
0 (-)
0 (-)
1 (6.7%)
Rash*
1 (6.7%)
0 (-)
Severe anemia
2 (13.3%)
0 (-)
Drug toxicity
1 (6.7%)
0 (-)
Virological failure
Lung nodule
Mood disorders
* Level 1
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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.
www.ias2013.org
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Acknowledgments
Patients of the HEPAVIH Cohort
Scientific 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-gastroentérologie / P Sogni; Anatomo-pathologie / B Terris, Z Makhlouf, G Dubost, F Tessier, L Gibault, F Beuvon, E Chambon, T Lazure; Virologie / A Krivine); CHU PitiéSalpétrière, 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 W innock.
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Back-up slides
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
HCV-RNA undetectable at W4 and W12
80
80 100
100%
60
60
67%
20
20
40
40
52%
1/8
0
Non
Relapsers
responders
100
60
40
80
100
80
60
69%
0/0
Non
Relapsers
responders
Naïve
100
80
64%
13%
0/0
5/5
60
60
80
100
Naïve
15/29
40
0
8/12
63%
Boceprevir
100
Telaprevir
40
40
47%
20/29
Cirrhotic
Noncirrhotic
1/6
20
0/2
Genotype Genotype
1A
1B
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0/4
1/4
Cirrhotic
Noncirrhotic
0
Genotype Genotype
1A
1B
8/17
0
7/11
0
0
20/32
17%
20
20
20
25%
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
Virological response
80
80%
60%
60
74%
60
69%
80
100
Boceprevir
100
Telaprevir
60%
40
20
20
40
44%
28/38
12/27
W4
W12
W24
W48
20%
2/10
6/10
6/10
W4
W12
W24
3/9
0
40/50
0
41/59
33%
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W48
Kuala Lumpur, Malaysia , 30 June - 3 July 2013
HCV-RNA undetectable at W12
100
Boceprevir
80
100%
85%
60%
60
74%
20
20
40
40
60
80 100
Telaprevir
0
100
80
100
Cirrhotic
Noncirrhotic
60
20
5/8
1/2
Genotype Genotype
1A
1B
www.ias2013.org
2/4
4/6
Cirrhotic
Noncirrhotic
0
27/32
50%
40
50%
40
13/18
0
Genotype Genotype
1A
1B
67%
63%
20
40
60
72%
0/0
Non
Relapsers
responders
80
84%
0
12/13
6/10
Naïve
20
40
20
27/34
0
Non
Relapsers
responders
80
79%
0/0
6/6
60
92%
60
80
100
Naïve
23/31
100
0
11/13
Kuala Lumpur, Malaysia , 30 June - 3 July 2013