Portal de Periódicos da CAPES

Transient CD4 cell recovery after hepatitis C virus cure in HIV /hepatitis C virus coinfected patients ( ANRS CO13 HEPAVIH cohort)

2024; Wiley; Linguagem: Inglês

10.1111/hiv.13752

1468-1293

Tangui Barré, Clémence Ramier, Karine Ory, Philippe Sogni, Hugues Aumaître, Tounes Saidi, Patrizia Carrieri, Fabienne Marcellin,

Hepatitis B Virus Studies

We read with great interest the recent work of Ryscavage et al. who described CD4 cell count evolution following direct-acting antivirals (DAA)-related hepatitis C virus (HCV) cure in HIV/HCV coinfected people [1]. They found an immediate transient increase in CD4 cell count after HCV treatment initiation, but no sustained effect. We tried to replicate their findings from the French ANRS CO13 HEPAVIH cohort [2]. From this prospective cohort of people coinfected with HIV and HCV, we selected participants cured from HCV (defined as a sustained virologic response 24 weeks after completing DAA treatment) with available CD4 cell count at least 6 months before and after DAA treatment initiation, and with no HIV viral load exceeding the detectability level (according to the laboratory test threshold) 36 months before and after DAA treatment initiation. As did Ryscavage et al., we performed an interrupted time analysis series analysis. Our study sample consisted of 176 participants (67.0% male), with a median (interquartile range [IQR]) age of 53 (50–56) years at the time of DAA initiation. Median (IQR) last CD4 cell count prior to DAA initiation was 529 (377–731) cells/mm3. Median CD4 cell count increased by 5.9% (p = 0.034; Figure 1) in the 6 months after DAA initiation, whereafter it decreased by 0.9% every 6 months (p = 0.053). Overall, there was no change in CD4 cell count in the post-DAA treatment period (−0.91 [−2.32, 0.51], p = 0.209). An immediate increase in CD4 cell count after HCV cure, as observed here, was not consistently reported in HIV/HCV coinfected people [3-5]. To the contrary, the absence of any effect of DAA-related HCV cure on CD4 cell count at 1 year post-cure seems to be more consistently documented [4-6]. A possible effect of cirrhosis on post-cure CD4 cell count change has also been inconsistently reported [1, 7]. HCV cure in people living with HIV may improve immune activation [8, 9]. However, further studies are needed to explore if this phenomenon may participate in CD4 change after HCV cure, and which other factors may contribute to it. As Ryscavage et al. did, we found a transient significant increase in CD4 cell count following HCV cure. Because of its transient nature and relatively small magnitude, the clinical significance of this increase is questionable. We agree with their conclusion that such changes should be explored in larger cohorts with longer follow-up period, and call for further research regarding factors associated with post-HCV cure immune recovery. Scientific Committee of the ANRS CO13 HEPAVIH Study Group: D. Salmon (Co-Principal Investigator), L. Wittkop (Co-Principal Investigator and Methodologist), P. Sogni (Co-Principal Investigator), P. Carrieri, B. Spire, K. Ory (Project Manager), P. Trimoulet, J. Izopet, L. Serfaty, L. Alric, M.A. Valantin, G. Pialoux, J. Chas, K. Barange, A. Naqvi, E. Rosenthal, A. Bicart-See, O. Bouchaud, A. Gervais, C. Lascoux-Combe, C. Goujard, K. Lacombe, C. Duvivier, D. Neau, P. Morlat, F. Bani-Sadr, F. Boufassa, C. Solas, H. Fontaine, L. Piroth, A. Simon, D. Zucman, F. Boué, P. Miailhes, E. Billaud, H. Aumaître, D. Rey, G. Peytavin, O. Zaeglel-Faucher, representative members of the sponsor (clinical research and pharmacovigilance department), representative members of patient organizations including TRT5. Clinical Centres (ward/participating physicians): APHP, Hôpitaux Universitaires Paris Centre, Paris (Médecine Interne et Maladies Infectieuses: D. Salmon, R. Usubillaga; Hépato-gastro-entérologie: P. Sogni, B. Bienvenu, O. Launay-Puybasset, C. Bernasconi, A. Brunet, B. Silbermann, H. Boucher, F. Rollot, O. Zak Dit Zbar, S. Pol, C. Le Jeunne-Ballif, P. Louergue, H. Mehawej, L. Merine-Belardi, F. Almasi, N. Benammar, L. Alagna, S. Chaussade, L. Guillevin; Anatomo-pathologie: B. Terris; Virologie: C. Norgeux); APHP Pitié-Salpétrière, Paris (Maladies Infectieuses et Tropicales: C. Katlama, M.A. Valantin, H. Stitou, F. Caby, L. Paris, L. Schneider, R. Tubiana; Médecine Interne: A. Simon, L. Roudière, O. Benveniste, G. Breton, M. Bonmarchand, M. Kirstetter; Anatomo-pathologie: F. Charlotte, F. Capron; Virologie: V. Calvez, V. Thibaut, C. Soulie, B. Abdi, S. Lambert-Niclot); APHM Sainte-Marguerite, Marseille (Immuno-Hématologie Clinique: S. Bregigeon-Ronot, O. Zaegel-Faucher, H. Laroche, A. Menard, E. Gaubert-Marechal; Virologie: S. Thirée, C. Tamalet, C. Hakimi; Anatomo-pathologie: J.C. Poluzzi; Pharmacologie: C. Solas); APHP Tenon, Paris (Maladies Infectieuses et Tropicales: G. Pialoux, J. Chas, L. Lassel, T. Lyavanc, S. Le Nagat, L. Slama, A. Canesti; Anatomo-pathologie: P. Callard; Virologie: B. Bachour); CHU Purpan, Toulouse (Médecine interne: L. Alric, N. Sigur, D. Bonnet, M. Guivarch; Hépato-gastro-entérologie: K. Barange, J.M. Peron, P. Massip, L. Cuzin, M. Obada, E. Bonnet, M. Alvarez, E. Labau, M. Mularczyk, N. Bourdoncle, J. Penecy, L. Porte, F. Busato, S. Khatibi, J. Bernard; Anatomo-pathologie: J. Selves; Virologie: F. Larroquette, V. Ferrer, J. Chiabrandon); CHU Archet, Nice (Médecine Interne: E. Rosenthal, C. Pradier, V. Mondain, P. Dellamonica, P.M. Roger, S. Ferrando, C. Ceppi; Infectiologie: A. Naqvi, V. Rio, B. Dunais, B. Prouvost, F. De Salvadore-Guillouet, I. Prebost, J. Durant, P. Pugliese; Anatomo-pathologie: J.F. Michels, M.C. Saint-Paul; Virologie: C. Partouche, K. Nerini); APHP Avicenne, Bobigny (Médecine Interne, Unité VIH: O. Bouchaud, S. Abgrall, I. Zamord, F. Bidegain, M. Azghay, C. Rouyer, M. Tatay, F. Mechai; Anatomo-pathologie: A. Martin; Virologie: Y. Baazia, V. Iwaka-Bande, A. Gerber); Hôpital Joseph Ducuing, Toulouse (Médecine Interne: A. Bicart-See, D. Garipuy, M.J. Ferro-Collados, F. Gaches; Virologie: F. Abravanel, F. Larroquette, J. Chiabrandon); APHP Bichat – Claude-Bernard, Paris (Maladies Infectieuses: A. Gervais, Y. Yazdanpanah; Anatomo-pathologie: D. Henin; Virologie: M. Bertine, M. Onambele; Pharmacologie: G. Peytavin); APHP Saint-Louis, Paris (Maladies infectieuses: C. Lascoux-Combe, T. Kandel, C. Pintado, J.M. Molina, C. Gatey, S. Gallien, W. Rozenbaum, M. Lafaurie, A.L. Munier, D. Ponscarme, M. Previllon, N. Colin De Verdière, M.G. Tateo; Virologie: P. Palmer, A. Gabassi, R. Amarsy, M.C. Mazeron); APHP Saint-Antoine (Maladies Infectieuses et Tropicales: K. Lacombe, J. Krause, P. Ingiliz, P.M. Girard, B. Lefebvre, N. Valin, M.C. Mehoyas, S. Fournier, J.L. Meynard, Z. Ouazene, H. Guyon, P. Roussard, F. Lallemand, G. Raguin, D. Bollens, M. Tourneur, H. Bideault, L. Fonquernie, J. Pacanowski; Anatomo-pathologie: D. Wendum; Virologie: D. Fofana, T. Thithuthuon); APHP, Hôpitaux Paris Sud, Bicêtre/Paul Brousse (Médecine Interne: C. Goujard, Y. Quertainmont, E. Teicher, L. Escaut, O. Derradji; Virologie: C. Pallier, F. Veillet, L. Mouna); APHP Necker, Paris (Maladies Infectieuses et Tropicales: O. Lortholary, C. Duvivier, C. Rouzaud, M. Shoai Tehrani, S. Boucly, G. Obenga, J.P. Viard; Virologie: E. Gardiennet, A. Mélard); CHU Bordeaux Hôpital Pellegrin, Bordeaux (Maladies Infectieuses et Tropicales: D. Neau, A. Ochoa, E. Blanchard, C. Cazanave, M. Dupon, H. Dutronc, F. Dauchy, H. Wille; Anatomo-pathologie: P. Bioulac-Sage; Virologie: P. Trimoulet); CHU Bordeaux Hôpital Saint-André, Bordeaux (Médecine Interne et Maladies Infectieuses: P. Morlat, D. Lacoste, F. Bonnet, N. Bernard, M. Hessamfar, F. Paccalin, C. Martell, M.C. Pertusa, M. Vandenhende, P. Mercié, T. Pistone, M.C. Receveur, M. Méchain, P. Duffau, C. Rivoisy, I. Faure, D. Malvy, J. Roger-Schmeltz, D. Dondia; Anatomo-pathologie: P. Bioulac-Sage; Virologie: P. Trimoulet); CHU Bordeaux Hôpital Haut-Levêque, Bordeaux (Médecine Interne: J.L. Pellegrin, E. Lazzaro; Anatomo-pathologie: P. Bioulac-Sage; Virologie: P. Trimoulet); Hôpital Foch, Suresnes (Médecine Interne: D. Zucman, C. Majerholc, J.E. Kahn, S. Hilaire; Virologie: M. Brollo); APHP Antoine Béclère, Clamart (Médecine Interne: F. Boué, S. Abgrall, J. Polo Devoto, I. Kansau, V. Chambrin, C. Pignon, C. Gatey, M. Favier; Virologie: C. Deback, C. Vauloup, C. Pailler, F. Veillet, L. Mouna); CHU Henri Mondor, Créteil (Immunologie Clinique: J.L. Lopez Zaragoza, Y. Lévy, J.D. Lelièvre, A.S. Lascaux, S. Scerra; Virologie: M. Bouvier-Alias); CHU Nantes Hôpital Hôtel Dieu, Nantes (Maladies Infectieuses et Tropicales: E. Billaud, F. Raffi, C. Allavena, V. Reliquet, D. Boutoille, C. Biron, M. Lefebvre, N. Hall, S. Bouchez, C. Bernaud, O. Mounoury; Virologie: A. Rodallec, L. Le Guen); Hôpital de la Croix Rousse, Lyon (Maladies Infectieuses et Tropicales: P. Miailhes, D. Peyramond, C. Chidiac, F. Ader, F. Biron, A. Boibieux, L. Cotte, T. Ferry, T. Perpoint, M. Amiri, F. Valour; Hépato-gastro-entérologie: J. Koffi, F. Zoulim, F. Bailly, P. Lack, M. Maynard, S. Radenne, C. Augustin-Normand; Virologie: E. Vassel, T.T. Le-Thi); CHU Dijon, Dijon (Infectiologie: L. Piroth, P. Chavanet, M. Duong Van Huyen, M. Buisson, A. Waldner-Combernoux, S. Mahy, A. Fillion); CH Perpignan, Perpignan (Maladies infectieuses et tropicales: H. Aumaître, M. Jean, A. Eden, M. Medus, M. Saada; Virologie: S. Gaba); CHU Robert Debré, Reims (Médecine interne, maladies infectieuses et immunologie clinique: F. Bani-Sadr, D. Lambert, Y. Nguyen, J.L. Berger, C. Rouger; Virologie: V. Brodard); CHRU Strasbourg (Le Trait d'Union: D. Rey, M. Partasani, C. Cheneau, M. Priester, C. Bernard-Henry, E. de Mautort; Virologie: A. Ertle, F. Jegou, A. Fush, P. Gantner, S. Fafi-Kremer). Data collection: L. Pinheiro, F. Roustand*, I. Kmiec, L. Traore*, S. Le Puil*, M.G. Tateo*, S. Benothame*, C. Pomes*, C. Louisin, M. Mole*, A. Adda, P. Thibaut, S. Poirier, R. Ben Rayana*, M.P. Pietri, V. Le Baut, Y. Cuvillier, M. Alabatanah*, F. Barret, F. Juster, C. Chesnel*, D. Beniken, M. Sebire-Le Cam, R. Monard, F. Badji*, S. Caldato, T. Rojas, A.S. Ritleng, A. Ivanova, L. Chalal, Z. Julia, M. Cavellec, C. Chevalier, E. Paredes-Manyari, S. Breau, N. Boughdiri, P. Fischer, C. Charles, S. Ogoudjobi, C. Brochier, V. Thoirain-Galvan, L. Traore, S. Chaussee, S. Benothmane, A. Sondro, O. Camou, V. Godard, M. Kai. Management, statistical analyses: C. Gilbert, M. Pailler, L. Merchadou, L. Esterle*, K. Ory, S. Gillet-Rousseau, C. Khan*, L. Abbad, M. Chalouni*, V. Conte, F. Marcellin, R. Knight, M. Mora, C. Protopopescu, P. Roux, T Barré. *Individuals who are no longer active but who participated in the cohort. We thank all study participants. This work was supported by the ANRS Emerging Infectious Diseases, with the participation of SIDACTION, Abbott France, Glaxo-Smith-Kline, Roche, Schering-Plough, BMS and Merck-Serono. The authors have no conflict of interest to declare concerning this work. The cohort was designed and implemented in accordance with the Declaration of Helsinki and was approved by the ethics committee of the Cochin University Hospital in Paris. All patients enrolled in the ANRS CO13 HEPAVIH cohort study provided written informed consent. Data available on request due to privacy/ethical restrictions.