1. 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 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

2. 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

3. 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

4. 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

5. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods (3) Rapid virological response (RVR 4 ): – Undetectable (<15 UI/mL) HCV-RNA at week 4 after initiation* Early virological response: - EVR 12 : Undetectable HCV-RNA at week 12* Severe anemia: - Hb <9 g/dL or a 4.5 g/dL decrease * of triple therapy

6. www.ias2013.org 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)

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

8. 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 (%) p Psychiatric disorders27 (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 treatment2 (1.8)9 (4.6) Cardiovascular disease3 (2.6)9 (4.4) Decompensated cirrhosis or HCC4 (3.5)7 (3.4) Platelets < 50 000/mm 3 3 (2.7)3 (1.5) Renal insufficiency3 (2.6)5 (2.4) Anemia (Hb <10 g/dL)2 (1.8)1 (0.5) At least one contra-indication to triple therapy39 (34.2)86 (41.7)0.191

9. 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 3 rd agent: Raltegravir: 43 Atazanavir: 22 Darunavir: 2 Saquinavir: 2 Lopinavir :2 Efavirenz: 7 Rilpivirine: 2

10. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 W4 W12 W24 W4 W12 W24 TelaprevirBoceprevir Results (5) Virological response

11. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Telaprevir Genotype 1B Results (6) Factors associated with VR 24 Boceprevir Naïve Non responders Relapsers Genotype 1A CirrhoticNon- cirrhotic Genotype 1B Naïve Non responders Relapsers Genotype 1A Cirrhotic Non- cirrhotic

12. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results (7) Virological response in cirrhotic non responders TelaprevirBoceprevir W4 W12 W24 W4 W12 W24

13. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Results (8) Virological response according to HAART Raltegravir AtazanavirEfavirenzOthers* * Others = Darunavir, Saquinavir, Rilpivirine, Lopinavir VR 24

14. 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. Telaprevir n=51 Boceprevir n=10 Anemia < 9 g/dl18 (35%)2 (20%) Rash8 (16%)0 (0%) Creatinine increase (µmol/L)+7 [-2,+10]+9 [+1,+33] Pneumopathy1 (2%)0 (-) Anal pruritus4 (8%)0 (-)

15. 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 failure10 (66.7%)4 (80%) Lung nodule1 (6.7%)0 (-) Mood disorders0 (-)1 (6.7%) Rash*1 (6.7%)0 (-) Severe anemia2 (13.3%)0 (-) Drug toxicity1 (6.7%)0 (-) * Level 1

16. 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.

17. 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-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.

18. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Back-up slides

19. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Telaprevir Genotype 1B Boceprevir Naïve Non responders Relapsers Genotype 1A CirrhoticNon- cirrhotic Genotype 1B Naïve Non responders Relapsers Genotype 1A Cirrhotic Non- cirrhotic HCV-RNA undetectable at W4 and W12

20. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Virological response W4 W12 W24W48 W4 W12 W24W48 TelaprevirBoceprevir

21. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Telaprevir Genotype 1B Boceprevir Naïve Non responders Relapsers Genotype 1A CirrhoticNon- cirrhotic Genotype 1B Naïve Non responders Relapsers Genotype 1A Cirrhotic Non- cirrhotic HCV-RNA undetectable at W12