Insights HIV/HCV coinfection: future scenarios, what Cohorts are doing, what can we do together

Transcription

1 Interactive Round Table among European Cohorts Insights HIV/HCV coinfection: future scenarios, what Cohorts are doing, what can we do together The ANRS CO13 HEPAVIH cohort PIs: D Salmon/F Dabis Methodologist: L. Wittkop

2 The ANRS CO13 HEPAVIH cohort partners ANRS

3 The ANRS CO13 HEPAVIH Cohort A cohort dedicated to HCV coinfection in France Created in 2005 with the general objective to better define the natural history of HIV/HCV co-infection in terms of morbidity and mortality. National multicenter cohort study 28 reference HIV clinical centres Reference labs involved in HIV and viral hepatitis Dedicated infrastructures (data, biobank) Strong implication of clinicians Follow-up facilitated by its adaptation on clinical guidelines Prospective data collection and constitution of a biobank.

4 Synopsis of HEPAVIH Cohort Inclusion period Target Population HIV/HCV co-infected patients Phase 1 Phase Phase 3 Phase 2 follow-up (co-infected patients under Boceprevir or Telaprevir) Possible extension of the followup period Standard follow-up co-infected patients including 200 healed after treatment, W0: treatment start W2W4, W8, W12, W16, W24, W36, W48, W60, W72, W96 Biobank: Each time - Once a year in non cirrhotic patients - Twice a year in cirrhotic patients Biobank: - Serum at inclusion & each year - Plasma at inclusion & each year - Whole blood at inclusion and M36 Phase 3 follow-up (HIV/HCV co-infected patients under a new anti-hcv molecule) W0: treatment start; W02 or W04 Visit at treatment stop Visit at 6 months after treatment stop Biobank: - Serum at W0 & W02/04 and at treatment stop - Plasma at W02 or W04

5 HEPAVIH cohort s characteristics part 1 DATA COLLECTED Demographics ROUTINARY Yearly Or every 6 months if cirrhotic IN A SUBGROUP HCVAb HCV genotype HCV genotypic sequencing/resistance Fib4 Fibroscan Liver disease staging Liver biopsy ART failure of DAA treatment (National Obserbvatory- Pr JM Pawlotsky) 10% of individuals (physician discretion)

6 Cohort s characteristics part 2 DAA DATA COLLECTED ROUTINARY Yearly Or every 6 months if cirrhotic HCV reinfection Hospitalisation Liver decompensation HCC Extrahepatic manifestations (cryoglobulinemia, lymphoma) HBsAg HBVDNA Biobank (plasma, serum) DNA if HBs Ag+ Yearly At inclusion in the cohort

7 Overview of inclusions (04/01/2016) N = st phase ( ): patients HCV chronically infected patients Median follow-up of 6 years 2nd phase ( ): 193 patients 1 st generation anti HCV PI - median follow-up of 1.5 year 3rd phase (since 26/05/2014): 476 patients Patients treated or to be treated with DAA (other than boceprevir or telaprevir)

8 Overview of inclusions with DAA (04/01/2016)

9 Specific objectives 3 rd phase - 5 research axis (Examples) 1) Clinical goals To identify factors associated with the outcome of liver disease (and non liver disease during treatment with new anti-hcv combinations in routine care settings. 2) Virological objectives To identify and characterize resistance mutations associated with treatment failure. 3) Pharmacological objectives To assess interactions between new anti-hcv drugs, anti-hiv drugs and Ribavirin. 4) Public Health objectives To describe access to these new drug combinations and their use in France, and to compare the psychosocial, behavioral, medical and biological characteristics of treated and untreated patients over time. 5) Methodological To adapt biostatistical methods already developed for the analysis of data from observational cohorts (marginal structural models, etc.) to the context of HIV/HCV co-infection, in order to estimate the effects of treatment and to determine the optimal timing of HCV treatment initiation. Other research axes interested in physiopathological, genetic questions could also be evolve.

10 Ongoing collaborations/ perspectives Needed to compare the course of HIV HCV coinfected patients with mono infected either with HIV or with HCV National collaborations AQUITAINE Cohort : HIV infected patients ANRS CO22 HEPATHER Therapeutic options for hepatitis B and/or C patients - Network of 33 HCV centers ANRS CO12 CIRVIR Cohort of cirrhotic patients 1500 patients - Network of HCV centers International collaborations COHERE in EuroCOORD (involved in > 20 projects, amongst others HCC project)

11 Back-up

12 Disease progression % First hepatic events cirrhotic patients % Mortality overall Mortality rate of 9% at 5 yea Time (years) Time (months) Hepatic events: Causes of death: Ascites, digestive hemorraghia, HCV related (43%) followed by hepatic Encephalopathia, HCC non AIDS defining cancers (14% (Foie et VIH 2014)

13 Response to DAA regimen (n=175) N=171 N=58 N=113 N=106 N=4 N=23 N=38

14 Response to DAA regimen N=117 N=26 N=15 N=13 N=125 N=45

15 Cure and hepatic disease evolution? (1) HIV/HCV co-infected patients with SVR had significantly more often a 30% decrease in liver stiffness (Fibroscan, results from Interferon alpha based regimen) Logrank 100 % Cumulative probability of achieving a decrease of liver stiffness SVR (n=53) Treatment Failure (n=46) 0 Follow-up (months) results have been confirmed using FIB4 values (AIDS 2015 published ahead of print)

16 Residual risk after cure Hepatic events and mortality after SVR Hepatic events Incidence/1000 PY (95%CI) Mortality Rate/1000 PY (95%CI) Overall (n=324) 4.17 ( ) 4.79 ( ) Patients F3/F4 (n=75) ( ) 3.70 ( ) Patients F0/F1/F2 (n=222) 2.02 ( ) 5.00 ( ) (Abstract 431 JNI 2015)

17 Acknowledgments All patients The ANRS CO13 HEPAVIH Study Group: Scientific committee: D Salmon (Investigator coordinator), F Dabis (co investigator coordinator), L Wittkop (scientific and methodological coordinator), L Esterle, P Sogni, P Trimoulet, J Izopet, V Paradis, B Spire, P Carrieri, C Katlama, G Pialoux, MA Valantin, J Chas, I Poizot- Martin, B Marchou, E Rosenthal, D Garipuy, O Bouchaud, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, A Bicart-See, C Duvivier, D Vittecoq, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, L Piroth, ML Chaix, F Abravanel, B Autran, AM Roque, C Solas, H Fontaine, L Serfaty, M Guiguet, G Chêne, D Costagliola, D Zucman, A Simon, S Dominguez, E Billaud, P Miailhes, J Polo Devoto, H Aumaître, D Rey, O Segeral, L Marchand (ANRS), S Couffin-Cadiergues (ANRS). Clinical Centers (ward / participating physicians): CHU Cochin, Paris (Médecine Interne et Maladies Infectieuses: D. Salmon, L. Alagna; Hépato-gastro-entérologie: P. Sogni; Anatomopathologie: B. Terris; Virologie: A. Krivine); CHU Pitié-Salpétrière, Paris (Maladies Infectieuses et Tropicales: C. Katlama, M.A. 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); CHU Sainte-Marguerite, Marseille (Service d'immuno-hématologie Clinique - CISIH: I. Poizot-Martin, O. Zaegel, M. Porcher; Virologie: C. Tamalet); CHU Tenon, Paris (Maladies Infectieuses et Tropicales: G. Pialoux, J. Chas, F. Bani-Sadr, L. Slama; 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; Anatomo-pathologie: J. Selves; Virologie: F. Larroquette); CHU Archet, Nice (Médecine Interne: E. Rosenthal; Infectiologie: J. Durant; Anatomo-pathologie: J. Haudebourg, M.C. Saint-Paul; Virologie: C. Partouche); 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, M.J. 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; Virologie: G. Alexandre); CHU Saint-Louis, Paris (Maladies infectieuses: J.M. Molina, C. Lascoux-Combe; Anatomo-pathologie: P. Bertheau, J. Duclos; Virologie: P. Palmer); CHU Saint-Antoine (Maladies Infectieuses et Tropicales: P.M. Girard, K. Lacombe, P. Campa; Anatomo-pathologie: D. Wendum, P. Cervera, J. Adam; Virologie: C. Viala); CHU Bicêtre, Paris (Médecine Interne: J.F. Delfraissy, C. Goujard, Y. Quertainmont; Virologie: C. Pallier); CHU Bicêtre, Paris (Maladies Infectieuses: D. Vittecoq); CHU Necker, Paris (Maladies Infectieuses et Tropicales: O. Lortholary, C. Duvivier, M. Shoai- Tehrani: Virologie: A. Mélard); CHU Pellegrin, Bordeaux (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.C. Receveur, S. Caldato; Anatomo-pathologie: P. Bioulac-Sage; Virologie: P. Trimoulet, S. Reigadas); Hôpital du Haut-Levêque, Bordeaux (Médecine Interne: J.L. Pellegrin, J.F. 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, J.D. Lelièvre, A.S. 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: T.T. Le-Thi); CHU Dijon, Dijon (Département d'infectiologie: P. Chavanet, L. Piroth, M. Duong Van Huyen, M. Buisson, A. Waldner-Combernoux, S. Mahy, R. Binois, A.L. Simonet-Lann, D. Croisier-Bertin); CHU Perpignan, Perpignan (Maladies infectieuses et tropicales: H. Aumaître); CHU Robert Debré, Reims (Médecine interne, maladies infectieuses et immunologie clinique: F. Bani-Sadr, D. Lambert, Y Nguen, C. Rouger, J.L. Berger); CHU Strasbourg (CISIH: D. Rey, M. Partrisiani, P. Gautner, M.L. Batard). Data collection: D. Beniken, C. Lupin, M. Guignard, M. Azar, P. Honoré, V. Payssan, S. Breau, A. Joulie, M. Mole, C. Bolliot, F. Touam, M. Shoai-Tehrani, F. André, J. Baume, H. Hue, L. Larmet, C. Brochier, V. Thoirain, M. Raho-Moussa, D. Bornarel, S. Gohier, C. Chesnel, G. Maradan, C. Taieb, S. Hadjoudj, M. Malet, I. Kmiec, P. Fischer. Data Management and Statistical analyses: O. Cheminat, J. Delaune, L. Dequae-Merchadou, N. Douiri, S. Gillet, C. Gilbert, A. Jacquet, R. Kherraz, C. Lions, P Lagorse, F. Marcellin, M. Mora, C. Moulaman, C. Protopopescu.