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1. Combined effects of smoking and HIV infection on the occurrence of aging-related manifestations

Author

Laurent Boyer, Sonia Zebachi, Sébastien Gallien, Laurent Margarit, Bruno Ribeiro Baptista, José-Luis Lopez-Zaragoza, Thomas D’Humières, Françoise Zerah, Sophie Hue, Geneviève Derumeaux, Serge Adnot, Etienne Audureau, and Jean-Daniel Lelièvre

Subjects
Medicine, Science
Abstract

Abstract Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with

Published
2023
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2. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author

Ilias I. Siempos, Andre C. Kalil, Drifa Belhadi, Viviane Cordeiro Veiga, Alexandre Biasi Cavalcanti, Westyn Branch-Elliman, Eleni Papoutsi, Konstantinos Gkirgkiris, Nikoleta A. Xixi, Anastasia Kotanidou, Olivier Hermine, Raphaël Porcher, Xavier Mariette, Philippe Ravaud, Serge Bureau, Maxime Dougados, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Annick Tibi, Elie Azoulay, Jacques Cadranel, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Karine Lacombe, Matthieu Mahevas, Frédéric Pene, Valerie Pourchet-Martinez, Frédéric Schlemmer, Yazdan Yazdanpanah, Gabriel Baron, Elodie Perrodeau, Damien Vanhoye, Cécile Kedzia, Lauren Demerville, Anne Gysembergh-Houal, Alexandre Bourgoin, Nabil Raked, Lakhdar Mameri, Claire Montlahuc, Lucie Biard, St.phanie Alary, Samir Hamiria, Thinhinane Bariz, Hala Semri, Dhiaa Meriem Hai, Moustafa Benafla, Mohamed Belloul, Pernelle Vauboin, Saskia Flamand, Claire Pacheco, Anouk Walter-Petrich, Emilia Stan, Souad Benarab, Corine Nyanou, Robin Charreteur, Céline Dupre, Kévin Cardet, Blandine Lehmann, Kamyl Baghli, Claire Madelaine, Eric D'Ortenzio, Oriane Puéchal, Caroline Semaille, Laurent Savale, Anatole Harrois, Samy Figueiredo, Jacques Duranteau, Nadia Anguel, Arthur Pavot, Xavier Monnet, Christian Richard, Jean-Louis Teboul, Philippe Durand, Pierre Tissieres, Mitja Jevnikar, David Montani, Stephan Pavy, Gaétane Nocturne, Samuel Bitoun, Nicolas Noel, Olivier Lambotte, Lelia Escaut, Stephane Jauréguiberry, Elodie Baudry, Christiane Verny, Edouard Lefevre, Mohamad Zaidan, Domitille Molinari, Gaël Leprun, Alain Fourreau, Laurent Cylly, Lamiae Grimaldi, Myriam Virlouvet, Ramdane Meftali, Soléne Fabre, Marion Licois, Asmaa Mamoune, Yacine Boudali, Clotilde Le Tiec, Céline Verstuyft, Anne-Marie Roques, Sophie Georgin-Lavialle, Patricia Senet, Gilles Pialoux, Angele Soria, Antoine Parrot, Helene François, Nathalie Rozensztajn, Emmanuelle Blin, Pascaline Choinier, Juliette Camuset, Jean-Simon Rech, Antony Canellas, Camille Rolland-Debord, Nadege Lemarié, Nicolas Belaube, Marine Nadal, Martin Siguier, Camille Petit-Hoang, Julie Chas, Elodie Drouet, Matthieu Lemoine, Audrey Phibel, Lucie Aunay, Eliane Bertrand, Sylviane Ravato, Marie Vayssettes, Anne Adda, Celine Wilpotte, Pélagie Thibaut, Julie Fillon, Isabelle Debrix, Soraya Fellahi, Jean-Philippe Bastard, Guillaume Lefévre, Jacques-Eric Gottenberg, Yves Hansmann, Frédéric Blanc, Sophie Ohlmann-Caillard, Vincent Castelain, Emmanuel Chatelus, Eva Chatron, Olivier Collange, François Danion, Frédéric De Blay, Pierre Diemunsch, Sophie Diemunsch, Renaud Felten, Bernard Goichot, Valentin Greigert, Aurelien Guffroy, Bob Heger, Charlotte Kaeuffer, Loic Kassegne, Anne Sophie Korganow, Pierrick Le Borgne, Nicolas Lefebvre, Paul-Michel Mertes, Eric Noll, Mathieu Oberlin, Vincent Poindron, Julien Pottecher, Yvon Ruch, François Weill, Nicolas Meyer, Emmanuel Andres, Eric Demonsant, Hakim Tayebi, Gabriel Nisand, Stéphane Brin, Cédric Sublon, Guillaume Becker, Anne Hutt, Tristan Martin, Sophie Bayer, Catherine Metzger, Arsene Mekinian, Noémie Abisror, Amir Adedjouma, Diane Bollens, Marion Bonneton, Nathalie Bourcicaux, Anne Bourrier, Maria Chauchard Thibault Chiarabiani, Doroth.e Chopin, Jonathan Cohen, Ines Devred, Bruno Donadille, Olivier Fain, Geoffrey Hariri, Vincent Jachiet, Patrick Ingliz, Marc Garnier, Marc Gatfosse, Etienne Ghrenassia, Delphine Gobert, Jessica Krause le Garrec, Cecilia Landman, Jean Remy Lavillegrand, Benedicte Lefebvre, Thibault Mahevas, Sandie Mazerand, Jean Luc Meynard, Marjolaine Morgand, Zineb Ouaz.ne, Jerome Pacanowski, S.bastien Riviere, Philippe Seksik, Harry Sokol, Heithem Soliman, Nadia Valin, Thomas Urbina, Chloé McAvoy, Maria Pereira Miranda, Gladys Aratus, Laurence Berard, Tabassome Simon, Anne Daguenel Nguyen, Elise Girault, Cl.mentine Mayala-Kanda, Marie Antignac, Céline Leplay, Jean-Benoit Arlet, Jean-Luc Diehl, Florence Bellenfant, Anne Blanchard, Alexandre Buffet, Bernard Cholley, Antoine Fayol, Edouard Flamarion, Anne Godier, Thomas Gorget, Sophie-Rym Hamada, Caroline Hauw-Berlemont, Jean-Sébastien Hulot, David Lebeaux, Marine Livrozet, Adrien Michon, Arthur Neuschwander, Marie-Aude Pennet, Benjamin Planquette, Brigitte Ranque, Olivier Sanchez, Geoffroy Volle, Sandrine Briois, Mathias Cornic, Virginie Elisee, Jesuthasan Denis, Juliette Djadi-Prat, Pauline Jouany, Ramon Junquera, Mickael Henriques, Amina Kebir, Isabelle Lehir, Jeanne Meunier, Florence Patin, Val.rie Paquet, Anne Tréhan, Véronique Vigna, Brigitte Sabatier, Damien Bergerot, Charléne Jouve, Camille Knosp, Olivia Lenoir, Nassim Mahtal, Léa Resmini, Xavier Lescure, Jade Ghosn, Antoine Bachelard, Anne Rachline, Valentina Isernia, Bao-chau, Phung, Dorothée Vallois, Aurelie Sautereau, Catherine Neukrich, Antoine Dossier, Raphaël Borie, Bruno Crestani, Gregory Ducrocq, Philippe Gabriel Steg, Philippe Dieude, Thomas Papo, Estelle Marcault, Marhaba Chaudhry, Charléne Da Silveira, Annabelle Metois, Ismahan Mahenni, Meriam Meziani, Cyndie Nilusmas, Sylvie Le Gac, Awa Ndiaye, Fran.oise Louni, Malikhone Chansombat, Zelie Julia, Solaya Chalal, Lynda Chalal, Laura Kramer, Jeniffer Le Grand, Kafif Ouifiya, Valentine Piquard, Sarah Tubiana, Yann Nguyen, Vasco Honsel, Emmanuel Weiss, Anais Codorniu, Virginie Zarrouk, Victoire de Lastours, Matthieu Uzzan, Naura Gamany, Agathe Claveirole, Alexandre Navid, Tiffanie Fouque, Yonathan Cohen, Maya Lupo, Constance Gilles, Roza Rahli, Zeina Louis, David Boutboul, Lionel Galicier, Yaël Amara, Gabrielle Archer, Amira Benattia, Anne Bergeron, Louise Bondeelle, Nathalie de Castro, Melissa Clément, Michaël Darmon, Blandine Denis, Clairelyne Dupin, Elsa Feredj, Delphine Feyeux, Adrien Joseph, Etienne Lenglin, Pierre Le Guen, Geoffroy Liégeon, Gwenaël Lorillon, Asma Mabrouki, Eric Mariotte, Grégoire Martin de Frémont, Adrien Mirouse, Jean-Michel Molina, Régis Peffault de Latour, Eric Oksenhendler, Julien Saussereau, Abdellatif Tazi, Jean-Jacques Tudesq, Lara Zafrani, Isabelle Brindele, Emmanuelle Bugnet, Karine Celli Lebras, Julien Chabert, Lamia Djaghout, Catherine Fauvaux, Anne Lise Jegu, Ewa Kozakiewicz, Martine Meunier, Marie-Thérèse Tremorin, Claire Davoine, Isabelle Madelaine, Sophie Caillat-Zucman, Constance Delaugerre, Florence Morin, Damien Sène, Ruxandra Burlacu, Benjamin Chousterman, Bruno Mégarbanne, Pascal Richette, Jean-Pierre Riveline, Aline Frazier, Eric Vicaut, Laure Berton, Tassadit Hadjam, Miguel Alejandro Vazquez-Ibarra, Clément Jourdaine, Olivia Tran, Véronique Jouis, Aude Jacob, Julie Smati, Stéphane Renaud, Claire Pernin, Lydia Suarez, Luca Semerano, Sébastien Abad, Ruben B. nainous, Nicolas Bonnet, Celine Comparon, Yves Cohen, Hugues Cordel, Robin Dhote, Nathalie Dournon, Boris Duchemann, Nathan Ebstein, Thomas Gille, Benedicte Giroux-Leprieur, Jeanne Goupil de Bouille, Hilario Nunes, Johanna Oziel, Dominique Roulot, Lucile Sese, ClaireTantet, Yurdagul Uzunhan, Coralie Bloch-Queyrat, Vincent Levy, Fadhila Messani, Mohammed Rahaoui, Myléne Petit, Sabrina Brahmi, Vanessa Rathoin, Marthe Rigal, Nathalie Costedoat-Chalumeau, Liem Binh Luong, Zakaria Ait Hamou, Sarah Benghanem, Philippe Blanche, Nicolas Carlier, Benjamin Chaigne, Remy Gauzit, Hassan Joumaa, Mathieu Jozwiak, Marie Lachétre, Hélène Lafoeste, Odie Launay, Paul Legendre, Jonathan Marey, Caroline Morbieu, Lola-Jade Palmieri, Tali-Anne Szwebel, Hendy Abdoul, Alexandra Bruneau, Audrey Beclin-Clabaux, Charly Larrieu, Pierre Montanari, Eric Dufour, Ada Clarke, Catherine Le Bourlout, Nathalie Marin, Nathalie Menage, Samira Saleh-Mghir, Mamadou Salif Cisse, Kahina Cheref, Corinne Guerin, Jérémie Zerbit, Marc Michel, Sébastien Gallien, Etienne Crickx, Benjamin Le Vavasseur, Emmanuelle Kempf, Karim Jaffal, William Vindrios, Julie Oniszczuk, Constance Guillaud, Pascal Lim, Elena Fois, Giovanna Melica, Marie Matignon, Maud Jalabert, Jean-Daniel Lelièvre, David Schmitz, Marion Bourhis, Sylia Belazouz, Laetitia Languille, Caroline Boucle, Nelly Cita, Agnés Didier, Fahem Froura, Katia Ledudal, Thiziri Sadaoui, Alaki Thiemele, Delphine Le Febvre De Bailly, Muriel Carvhalo Verlinde, Julien Mayaux, Patrice Cacoub, David Saadoun, Mathieu Vautier, Héléne Bugaut, Olivier Benveniste, Yves Allenbach, Gaëlle Leroux, Aude Rigolet, Perrine Guillaume-Jugnot, Fanny Domont, Anne Claire Desbois, Chloé Comarmond, Nicolas Champtiaux, Segolene Toquet, Amine Ghembaza, Matheus Vieira, Georgina Maalouf, Goncalo Boleto, Yasmina Ferfar, Jean-Christophe Corvol, C.line Louapre, Sara Sambin, Louise-Laure Mariani, Carine Karachi, Florence Tubach, Candice Estellat, Linda Gimeno, Karine Martin, Aicha Bah, Vixra Keo, Sabrine Ouamri, Yasmine Messaoudi, Nessima Yelles, Pierre Faye, Sebastien Cavelot, Cecile Larcheveque, Laurence Annonay, Jaouad Benhida, Aida Zahrate-Ghoul, Soumeya Hammal, Ridha Belilita, Fanny Charbonnier, Claire Aguilar, Fanny Alby-Laurent, Carole Burger, Clara Campos-Vega, Nathalie Chavarot, Benjamin Fournier, Claire Rouzaud, Damien Vimpére, Caroline Elie, Prissile Bakouboula, Laure Choupeaux, Sophie Granville, Elodie Issorat, Christine Broissand, Marie-Alexandra Alyanakian, Guillaume Geri, Nawal Derridj, Naima Sguiouar, Hakim Meddah, Mourad Djadel, Héléne Chambrin-Lauvray, Jean-Charles Duclos-vallée, Faouzi Saliba, Sophie-Caroline Sacleux, Ilias Kounis, Sonia Tamazirt, Eric Rudant, Jean-Marie Michot, Annabelle Stoclin, Emeline Colomba, Fanny Pommeret, Christophe Willekens, Rosa Da Silva, Valérie Dejean, Yasmina Mekid, Ines Ben-Mabrouk, Florence Netzer, Caroline Pradon, Laurence Drouard, Valérie Camara-Clayette, Alexandre Morel, Gilles Garcia, Abolfazl Mohebbi, Férial Berbour, Mélanie Dehais, Anne-Lise Pouliquen, Alison Klasen, Loren Soyez-Herkert, Jonathan London, Younes Keroumi, Emmanuelle Guillot, Guillaume Grailles, Younes El amine, Fanny Defrancq, Hanane Fodil, Chaouki Bouras, Dominique Dautel, Nicolas Gambier, Thierno Dieye, Boris Bienvenu, Victor Lancon, Laurence Lecomte, Kristina Beziriganyan, Belkacem Asselate, Laure Allanic, Elena Kiouris, Marie-Héléne Legros, Christine Lemagner, Pascal Martel, Vincent Provitolo, Félix Ackermann, Mathilde Le Marchand, Aurélie Chan Hew Wai, Dimitri Fremont, Elisabeth Coupez, Mireille Adda, Frédéric Duée, Lise Bernard, Antoine Gros, Estelle Henry, Claire Courtin, Anne Pattyn, Pierre-Grégoire Guinot, Marc Bardou, Agnes Maurer, Julie Jambon, Amélie Cransac, Corinne Pernot, Bruno Mourvillier, Eric Marquis, Philippe Benoit, Damien Roux, Coralie Gernez, Cécile Yelnik, Julien Poissy, Mandy Nizard, Fanette Denies, Helene Gros, Jean-Jacques Mourad, Emmanuelle Sacco, Sophie Renet, F. Ader, Y. Yazdanpanah, F. Mentre, N. Peiffer-Smadja, F.X. Lescure, J. Poissy, L. Bouadma, J.F. Timsit, B. Lina, F. Morfin-Sherpa, M. Bouscambert, A. Gaymard, G. Peytavin, L. Abel, J. Guedj, C. Andrejak, C. Burdet, C. Laouenan, D. Belhadi, A. Dupont, T. Alfaiate, B. Basli, A. Chair, S. Laribi, J. Level, M. Schneider, M.C. Tellier, A. Dechanet, D. Costagliola, B. Terrier, M. Ohana, S. Couffin-Cadiergues, H. Esperou, C. Delmas, J. Saillard, C. Fougerou, L. Moinot, L. Wittkop, C. Cagnot, S. Le Mestre, D. Lebrasseur-Longuet, V. Petrov-Sanchez, A. Diallo, N. Mercier, V. Icard, B. Leveau, S. Tubiana, B. Hamze, A. Gelley, M. Noret, E. D’Ortenzio, O. Puechal, C. Semaille, T. Welte, J.A. Paiva, M. Halanova, M.P. Kieny, E. Balssa, C. Birkle, S. Gibowski, E. Landry, A. Le Goff, L. Moachon, C. Moins, L. Wadouachi, C. Paul, A. Levier, D. Bougon, F. Djossou, L. Epelboin, J. Dellamonica, C.H. Marquette, C. Robert, S. Gibot, E. Senneville, V. Jean-Michel, Y. Zerbib, C. Chirouze, A. Boyer, C. Cazanave, D. Gruson, D. Malvy, P. Andreu, J.P. Quenot, N. Terzi, K. Faure, C. Chabartier, V. Le Moing, K. Klouche, T. Ferry, F, Valour, B. Gaborit, E. Canet, P. Le Turnier, D. Boutoille, F. Bani-Sadr, F. Benezit, M. Revest, C. Cameli, A. Caro, MJ Ngo Um Tegue, Y. Le Tulzo, B. Laviolle, F. Laine, G. Thiery, F. Meziani, Y. Hansmann, W. Oulehri, C. Tacquard, F. Vardon-Bounes, B. Riu-Poulenc, M. Murris-Espin, L. Bernard, D. Garot, O. Hinschberger, M. Martinot, C. Bruel, B. Pilmis, O. Bouchaud, P. Loubet, C. Roger, X. Monnet, S. Figueiredo, V. Godard, J.P. Mira, M. Lachatre, S. Kerneis, J. Aboab, N. Sayre, F. Crockett, D. Lebeaux, A. Buffet, J.L. Diehl, A. Fayol, J.S. Hulot, M. Livrozet, A Mekontso- Dessap, C. Ficko, F. Stefan, J. Le Pavec, J. Mayaux, H. Ait-Oufella, J.M. Molina, G. Pialoux, M. Fartoukh, J. Textoris, M. Brossard, A. Essat, E. Netzer, Y. Riault, M. Ghislain, L. Beniguel, M. Genin, L. Gouichiche, C. Betard, L. Belkhir, A. Altdorfer, V Fraipont Centro, S. Braz, JM Ferreira Ribeiro, R Roncon Alburqueque, M. Berna, M. Alexandre, B. Lamprecht, A. Egle, R. Greil, M. Joannidis, Thomas F. Patterson, Philip O. Ponce, Barbara S. Taylor, Jan E. Patterson, Jason E. Bowling, Heta Javeri, LuAnn Larson, Angela Hewlett, Aneesh K. Mehta, Nadine G. Rouphael, Youssef Saklawi, Nicholas Scanlon, Jessica J. Traenkner, Ronald P. Trible, Jr., Emmanuel B. Walter, Noel Ivey, Thomas L. Holland, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Helen S. Lee, Susan Kline, Joanne Billings, Brooke Noren, Hyun Kim, Tyler D. Bold, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Nicole Iovine, Lars K. Beattie, Rebecca Murray Wakeman, Matthew Shaw, Mamta K. Jain, Satish Mocherla, Jessica Meisner, Amneris Luque, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, Ann R. Falsey, Angela R. Branche, Cheryl Rozario, Justino Regalado Pineda, José Arturo Martinez-Orozco, David Chien Lye, Sean WX. Ong, Po Ying Chia, Barnaby E. Young, Uriel Sandkovsky, Mezgebe Berhe, Clinton Haley, Emma Dishner, Valeria D. Cantos, Colleen F. Kelley, Paulina A. Rebolledo Esteinou, Sheetal Kandiah, Sarah B. Doernberg, Pierre-Cedric B. Crouch, Hannah Jang, Anne F. Luetkemeyer, Jay Dwyer, Stuart H. Cohen, George R. Thompson, 3rd, Hien H. Nguyen, Robert W. Finberg, Jennifer P. Wang, Juan Perez-Velazquez, Mireya Wessolossky, Patrick E.H. Jackson, Taison D. Bell, Miranda J. West, Babafemi Taiwo, Karen Krueger, Johnny Perez, Triniece Pearson, Catharine I. Paules, Kathleen G. Julian, Danish Ahmad, Alexander G. Hajduczok, Henry Arguinchona, Christa Arguinchona, Nathaniel Erdmann, Paul Goepfert, Neera Ahuja, Maria G. Frank, David Wyles, Heather Young, Myoung-don Oh, Wan Beom Park, Chang Kyung Kang, Vincent Marconi, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Eu Suk Kim, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Seow Yen Tan, Humaira Shafi, MF Jaime Chien, Raymond KC. Fong, Daniel D. Murray, Jens Lundgren, Henrik Nielsen, Tomas Jensen, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Otto O. Yang, Jenny Ahn, Rubi Arias, Rekha R. Rapaka, Naomi Hauser, James D. Campbell, William R. Short, Pablo Tebas, Jillian T. Baron, Susan L.F. McLellan, Lucas S. Blanton, Justin B. Seashore, C. Buddy Creech, Todd W. Rice, Shannon Walker, Isaac P. Thomsen, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Surinder Kaur Pada, Alvin DY. Wang, Li Lin, Michelle Harkins, Gregory Mertz, Nestor Sosa, Louis Yi Ann Chai, Paul Anantharajah Tambyah, Sai Meng Tham, Sophia Archuleta, Gabriel Yan, David A. Lindholm, Ana Elizabeth Markelz, Katrin Mende, Richard Mularski, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Ryan C. Maves, Gregory C. Utz, Sarah L. George, Daniel F. Hoft, James D. Brien, Roger Paredes, Lourdes Mateu, Cora Loste, Princy Kumar, Sarah Thornton, Sharmila Mohanraj, Noreen A. Hynes, Lauren M. Sauer, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Susan E. Chambers, Richard M. Novak, Andrea Wendrow, Samir K. Gupta, Tida Lee, Tahaniyat Lalani, Mark Holodniy, Aarthi Chary, Nikhil Huprikar, Anuradha Ganesan, Norio Ohmagari, Ayako Mikami, D. Ashley Price, Christopher J.A. Duncan, Kerry Dierberg, Henry J. Neumann, Stephanie N. Taylor, Alisha Lacour, Najy Masri, Edwin Swiatlo, Kyle Widmer, James D. Neaton, Mary Bessesen, David S. Stephens, Timothy H. Burgess, Timothy M. Uyeki, Robert Walker, G. Lynn Marks, Anu Osinusi, Huyen Cao, Anabela Cardoso, Stephanie de Bono, Douglas E. Schlichting, Kevin K. Chung, Jennifer L. Ferreira, Michelle Green, Mat Makowski, Michael R. Wierzbicki, Tom M. Conrad, Jill Ann El-Khorazaty, Heather Hill, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, John H. Beigel, Kay M. Tomashek, Varduhi Ghazaryan, Tatiana Beresnev, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, Ruth Florese, Jocelyn D. Voell, Richard Davey, Ruth C. Serrano, Zanthia Wiley, Varun K. Phadke, Paul A. Goepfert, Carlos A. Gomez, Theresa A. Sofarelli, Laura Certain, Hannah N. Imlay, Cameron R. Wolfe, Emily R. Ko, John J. Engemann, Nora Bautista Felix, Claire R. Wan, Sammy T. Elmor, Laurel R. Bristow, Michelle S. Harkins, Nicole M. Iovine, Marie-Carmelle Elie-Turenne, Victor F. Tapson, Pyoeng Gyun Choe, Richard A. Mularski, Kevin S. Rhie, Rezhan H. Hussein, Dilek Ince, Patricia L. Winokur, Jin Takasaki, Sho Saito, Kimberly McConnell, PharmD, David L. Wyles, Ellen Sarcone, Kevin A. Grimes, Katherine Perez, Charles Janak, Jennifer A. Whitaker, Paulina A. Rebolledo, John Gharbin, Allison A. Lambert, Diego F. Zea, Emma Bainbridge, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, Evelyn Ling, Minjoung Go, Fleesie A. Hubbard, Melony Chakrabarty, Maryrose Laguio-Vila, Edward E. Walsh, Faheem Guirgis, Vincent C. Marconi, Christian Madar, Scott A. Borgetti, Corri Levine, Joy Nock, Keith Candiotti, Julia Rozman, Fernando Dangond, Yann Hyvert, Andrea Seitzinger, Kaitlyn Cross, Stephanie Pettibone, Seema U. Nayak, and Gregory A. Deye

Subjects
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Published
2024
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3. Long-Term Clinical Safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: A Prospective, Multi-Country, Observational Study

Author

Adeep Puri, Andrew J. Pollard, Catherine Schmidt-Mutter, Fabrice Lainé, George PrayGod, Hannah Kibuuka, Houreratou Barry, Jean-François Nicolas, Jean-Daniel Lelièvre, Sodiomon Bienvenu Sirima, Beatrice Kamala, Daniela Manno, Deborah Watson-Jones, Auguste Gaddah, Babajide Keshinro, Kerstin Luhn, Cynthia Robinson, and Macaya Douoguih

Subjects
Ebola virus, Ad26.ZEBOV, MVA-BN-Filo, vaccines, clinical trials, safety, Medicine
Abstract

In this prospective, observational study (ClinicalTrials.gov Identifier: NCT02661464), long-term safety information was collected from participants previously exposed to the Ebola vaccines Ad26.ZEBOV and/or MVA-BN-Filo while enrolled in phase 1, 2, or 3 clinical studies. The study was conducted at 15 sites in seven countries (Burkina Faso, France, Kenya, Tanzania, Uganda, the United Kingdom, and the United States). Adult participants and offspring from vaccinated female participants who became pregnant (estimated conception ≤28 days after vaccination with MVA-BN-Filo or ≤3 months after vaccination with Ad26.ZEBOV) were enrolled. Adults were followed for 60 months after their first vaccination, and children born to female participants were followed for 60 months after birth. In the full analysis set (n = 614 adults; median age [range]: 32.0 [18–65] years), 49 (8.0%) had ≥1 serious adverse event (SAE); the incidence rate of any SAE was 27.4 per 1000 person-years (95% confidence interval: 21.0, 35.2). The unrelated SAEs of malaria were reported in the two infants in the full analysis set, aged 11 and 18 months; both episodes were resolved. No deaths or life-threatening SAEs occurred during the study. Overall, no major safety issues were identified; one related SAE was reported. These findings support the long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo vaccines.

Published
2024
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4. Neutralizing antibodies against SARS-CoV-2 variants following mRNA booster vaccination in adults older than 65 years

Author

Christine Durier, Laetitia Ninove, Maeva Lefebvre, Anne Radenne, Corinne Desaint, Jacques Ropers, Rebecca Bauer, Said Lebbah, Diane Carette, Marie Lachatre, Anne-Sophie Lecompte, Dominique Deplanque, Elisabeth Botelho-Nevers, Anne Conrad, Bertrand Dussol, Zoha Maakaroun-Vermesse, Giovanna Melica, Jean-François Nicolas, Renaud Verdon, Jacques Kiladjian, Paul Loubet, Catherine Schmidt-Mutter, Christian Dualé, Séverine Ansart, Stéphane Priet, Axel Levier, Diana Molino, Louis-Victorien Vieillard, Béatrice Parfait, Jean-Daniel Lelièvre, Eric Tartour, Xavier de Lamballerie, Odile Launay, ANRS0002S CoviCompareP Group, AP-HP CoviCompareM Group, Biological resource centers, Laboratories, Trial coordination, Sponsor, and Scientific Committee

Subjects
Medicine, Science
Abstract

Abstract Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65–84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost.

Published
2022
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5. Single-cell RNA-seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells

Author

Flavien Brouiller, Francesca Nadalin, Pierre-Emmanuel Bonté, Ouardia Ait-Mohamed, Constance Delaugerre, Jean-Daniel Lelièvre, Florent Ginhoux, Nicolas Ruffin, and Philippe Benaroch

Subjects
Biological sciences, Clinical microbiology, Microbiology, Molecular biology, Transcriptomics, Science
Abstract

Summary: Sensing of incoming viruses is a pivotal task of dendritic cells (DCs). Human primary blood DCs encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of the blood Axl+DC subset, endowed with unique capacities to bind, replicate, and transmit HIV-1 prompted us to evaluate its anti-viral response. We demonstrate that HIV-1 induced two main broad and intense transcriptional programs in different Axl+DCs potentially induced by different sensors; an NF-κB-mediated program that led to DC maturation and efficient CD4+ T cell activation, and a program mediated by STAT1/2 that activated type I IFN and ISG responses. These responses were absent from cDC2 exposed to HIV-1 except when viral replication was allowed. Finally, Axl+DCs actively replicating HIV-1 identified by quantification of viral transcripts exhibited a mixed NF-κB/ISG innate response. Our results suggest that the route of HIV-1 entry may dictate different innate sensing pathways by DCs.

Published
2023
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6. Impact of a Dedicated Pretransplant Infectious Disease Consultation on Respiratory Tract Infections in Kidney Allograft Recipients: A Retrospective Study of 516 Recipients

Author

Elsa Feredj, Etienne Audureau, Anna Boueilh, Vincent Fihman, Slim Fourati, Jean-Daniel Lelièvre, Sébastien Gallien, Philippe Grimbert, Marie Matignon, and Giovanna Melica

Subjects
vaccination, pneumonia, kidney transplantation, Medicine
Abstract

Background: Respiratory tract infections (RTIs) are a leading cause of death after kidney transplant. Preventive strategies may be implemented during a dedicated infectious disease consultation (IDC) before transplantation. Impact of IDC on RTIs after transplant has not been determined. Methods: We conducted a monocentric retrospective cohort analysis including all kidney transplant recipients from January 2015 to December 2019. We evaluated the impact of IDC on RTIs and identified risk and protective factors associated with RTIs. Results: We included 516 kidney transplant recipients. Among these, 145 had an IDC before transplant. Ninety-five patients presented 123 RTIs, including 75 (61%) with pneumonia. Patient that benefited from IDC presented significantly less RTIs (p = 0.049). RTIs were an independent risk factor of mortality (HR = 3.64 (1.97–6.73)). Independent risk factors for RTIs included HIV (OR = 3.33 (1.43–7.74)) and HCV (OR = 3.76 (1.58–8.96)). IDC was identified as an independent protective factor (OR = 0.48 (0.26–0.88)). IDC prior to transplantation is associated with diminished RTIs and is an independent protective factor. RTIs after kidney transplant are an independent risk factor of death. Implementing systematic IDC may have an important impact on reducing RTIs and related morbidity and mortality.

Published
2023
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7. Targeting human langerin promotes HIV-1 specific humoral immune responses.

Author

Jérôme Kervevan, Aurélie Bouteau, Juliane S Lanza, Adele Hammoudi, Sandra Zurawski, Mathieu Surenaud, Lydie Dieudonné, Marion Bonnet, Cécile Lefebvre, Hakim Hocini, Romain Marlin, Aurélie Guguin, Barbara Hersant, Oana Hermeziu, Elisabeth Menu, Christine Lacabaratz, Jean-Daniel Lelièvre, Gerard Zurawski, Véronique Godot, Sandrine Henri, Botond Z Igyártó, Yves Levy, and Sylvain Cardinaud

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and in vitro differentiated LC induce differentiation and expansion of naïve CD4+ T cells into T follicular helper (Tfh) cells. Second, when human LC are pre-treated with αLC.Env, differentiated Tfh cells significantly promote the production of specific IgG by B cells. Strikingly, HIV-Env-specific Ig are secreted by HIV-specific memory B cells. Consistently, we found that receptors and cytokines involved in Tfh differentiation and B cell functions are upregulated by LC during their maturation and after targeting Langerin. Finally, we show that subcutaneous immunization of mice by αLC.Env induces germinal center (GC) reaction in draining lymph nodes with higher numbers of Tfh cells, Env-specific B cells, as well as specific IgG serum levels compared to mice immunized with the non-targeting Env antigen. Altogether, we provide evidence that human LC properly targeted may be licensed to efficiently induce Tfh cell and B cell responses in GC.

Published
2021
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8. Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis.

Author

Marie Armani-Tourret, Zhicheng Zhou, Romain Gasser, Isabelle Staropoli, Vincent Cantaloube-Ferrieu, Yann Benureau, Javier Garcia-Perez, Mayte Pérez-Olmeda, Valérie Lorin, Bénédicte Puissant-Lubrano, Lambert Assoumou, Constance Delaugerre, Jean-Daniel Lelièvre, Yves Lévy, Hugo Mouquet, Guillaume Martin-Blondel, Jose Alcami, Fernando Arenzana-Seisdedos, Jacques Izopet, Philippe Colin, and Bernard Lagane

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses' receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART.

Published
2021
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9. Viral genomic, metagenomic and human transcriptomic characterization and prediction of the clinical forms of COVID-19.

Author

Christophe Rodriguez, Nicolas de Prost, Slim Fourati, Claudie Lamoureux, Guillaume Gricourt, Melissa N'debi, Florence Canoui-Poitrine, Isaac Désveaux, Oriane Picard, Vanessa Demontant, Elisabeth Trawinski, Raphaël Lepeule, Laure Surgers, William Vindrios, Jean-Daniel Lelièvre, Nicolas Mongardon, Olivier Langeron, José L Cohen, Armand Mekontso-Dessap, Paul-Louis Woerther, and Jean-Michel Pawlotsky

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper "Th1-Th17" profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19.

Published
2021
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10. TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice.

Author

Véronique Godot, Colas Tcherakian, Laurine Gil, Iñaki Cervera-Marzal, Guangming Li, Liang Cheng, Nicolas Ortonne, Jean-Daniel Lelièvre, Giuseppe Pantaleo, Craig Fenwick, Mireille Centlivre, Hugo Mouquet, Sylvain Cardinaud, Sandra M Zurawski, Gerard Zurawski, Pierre Milpied, Lishan Su, and Yves Lévy

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans.

Published
2020
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11. Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.

Author

Yves Lévy, Christine Lacabaratz, Kim Ellefsen-Lavoie, Wolfgang Stöhr, Jean-Daniel Lelièvre, Pierre-Alexandre Bart, Odile Launay, Jonathan Weber, Bernd Salzberger, Aurélie Wiedemann, Mathieu Surenaud, David M Koelle, Hans Wolf, Ralf Wagner, Véronique Rieux, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Raphael Gottardo, Bryan Mayer, Song Ding, Rodolphe Thiébaut, Sheena McCormack, Geneviève Chêne, and Giuseppe Pantaleo

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P

Published
2020
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12. Functional Ex Vivo Testing of Alveolar Monocytes in Patients with Pneumonia-Related ARDS

Author

Inès Bendib, Asma Beldi-Ferchiou, Frédéric Schlemmer, Bernard Maitre, Mathieu Surenaud, Sophie Hüe, Guillaume Carteaux, Keyvan Razazi, Jean-Daniel Lelièvre, Yves Lévy, Armand Mekontso Dessap, Véronique Godot, and Nicolas de Prost

Subjects
acute respiratory distress syndrome, pneumonia, HLA-DR, TNF, phagocytosis, Cytology, QH573-671
Abstract

Biomarkers of disease severity might help with individualizing the management of patients with acute respiratory distress syndrome (ARDS). During sepsis, a sustained decreased expression of the antigen-presenting molecule human leucocyte antigen-DR (HLA-DR) on circulating monocytes is used as a surrogate marker of immune failure. This study aimed at assessing whether HLA-DR expression on alveolar monocytes in the setting of a severe lung infection is associated with their functional alterations. BAL fluid and blood from immunocompetent patients with pneumonia-related ARDS admitted between 2016 and 2018 were isolated in a prospective monocentric study. Alveolar and blood monocytes were immunophenotyped using flow cytometry. Functional tests were performed on alveolar and blood monocytes after in vitro lipopolysaccharide (LPS) stimulation. Phagocytosis activity and intracellular tumor necrosis factor (TNF) production were quantified using fluorochrome-conjugated-specific antibodies. Ten ARDS and seven non-ARDS control patients were included. Patients with pneumonia-related ARDS exhibited significantly lower HLA-DR expression both on circulating (p < 0.0001) and alveolar (p = 0.0002) monocytes. There was no statistically significant difference observed between patient groups (ARDS vs. non-ARDS) regarding both alveolar and blood monocytes phagocytosis activity. After LPS stimulation, alveolar (p = 0.027) and blood (p = 0.005) monocytes from pneumonia-related ARDS patients had a significantly lower intracellular TNF expression than non-ARDS patients. Monocytes from pneumonia-related ARDS patients have a deactivated status and an impaired TNF production capacity but display potent phagocytic activity. HLA-DR level expression should not be used as a surrogate marker of the phagocytic activity or the TNF production capacity of alveolar monocytes.

Published
2021
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13. Development of an epitope-based HIV-1 vaccine strategy from HIV-1 lipopeptide to dendritic-based vaccines

Author

Mathieu Surenaud, Christine Lacabaratz, Gérard Zurawski, Yves Lévy, and Jean-Daniel Lelièvre

Subjects
dc-targeting, epitope, hiv-1, immunogenicity, lipopeptide, vaccine, Internal medicine, RC31-1245
Abstract

Introduction: Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.

Published
2017
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14. Anti-HIV potency of T-cell responses elicited by dendritic cell therapeutic vaccination.

Author

Mathieu Surenaud, Monica Montes, Cecilia S Lindestam Arlehamn, Alessandro Sette, Jacques Banchereau, Karolina Palucka, Jean-Daniel Lelièvre, Christine Lacabaratz, and Yves Lévy

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Identification and characterization of CD8+ and CD4+ T-cell epitopes elicited by HIV therapeutic vaccination is key for elucidating the nature of protective cellular responses and mechanism of the immune evasion of HIV. Here, we report the characterization of HIV-specific T-cell responses in cART (combination antiretroviral therapy) treated HIV-1 infected patients after vaccination with ex vivo-generated IFNα Dendritic Cells (DCs) loaded with LIPO-5 (HIV-1 Nef 66-97, Nef 116-145, Gag 17-35, Gag 253-284 and Pol 325-355 lipopeptides). Vaccination induced and/or expanded HIV-specific CD8+ T cells producing IFNγ, perforin, granzyme A and granzyme B, and also CD4+ T cells secreting IFNγ, IL-2 and IL-13. These responses were directed against dominant and subdominant epitopes representing all vaccine regions; Gag, Pol and Nef. Interestingly, IL-2 and IL-13 produced by CD4+ T cells were negatively correlated with the peak of viral replication following analytic treatment interruption (ATI). Epitope mapping confirmed that vaccination elicited responses against predicted T-cell epitopes, but also allowed to identify a set of 8 new HIV-1 HLA-DR-restricted CD4+ T-cell epitopes. These results may help to better design future DC therapeutic vaccines and underscore the role of vaccine-elicited CD4+ T-cell responses to achieve control of HIV replication.

Published
2019
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15. Proliferative memory SAMHD1low CD4+ T cells harbour high levels of HIV-1 with compartmentalized viral populations.

Author

Lylia Hani, Antoine Chaillon, Marie-Laure Nere, Nicolas Ruffin, Joudy Alameddine, Maud Salmona, José-Luiz Lopez Zaragoza, Davey M Smith, Olivier Schwartz, Jean-Daniel Lelièvre, Constance Delaugerre, Yves Lévy, and Nabila Seddiki

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

We previously reported the presence of memory CD4+ T cells that express low levels of SAMHD1 (SAMHD1low) in peripheral blood and lymph nodes from both HIV-1 infected and uninfected individuals. These cells are enriched in Th17 and Tfh subsets, two populations known to be preferentially targeted by HIV-1. Here we investigated whether SAMHD1low CD4+ T-cells harbour replication-competent virus and compartimentalized HIV-1 genomes. We sorted memory CD4+CD45RO+SAMHD1low, CD4+CD45RO+SAMHD1+ and naive CD4+CD45RO-SAMHD1+ cells from HIV-1-infected patients on anti-retroviral therapy (c-ART) and performed HIV-1 DNA quantification, ultra-deep-sequencing of partial env (C2/V3) sequences and phenotypic characterization of the cells. We show that SAMHD1low cells include novel Th17 CCR6+ subsets that lack CXCR3 and CCR4 (CCR6+DN). There is a decrease of the % of Th17 in SAMHD1low compartment in infected compared to uninfected individuals (41% vs 55%, p

Published
2019
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16. HIV-1 prophylactic vaccines: state of the art

Author

Jean-Daniel Lelièvre and Yves Lévy

Subjects
Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Abstract

The quest for an effective HIV-1 vaccine began early in the course of the HIV pandemic. Over time, the paradigm has evolved from B cell- towards T cell-based vaccines. Results from initial Phase II/III trials have been disappointing; however, while modest, the unexpected results of the Phase II/III RV144 trial in Thailand have re-energised the field. Indeed a clear correlation was demonstrated in this trial between protection and immunological biomarkers, namely non-neutralising antibodies against the V1V2 region.Recent data obtained from cohorts of recently HIV-1-infected individuals have enabled exploration of the role of neutralising antibodies and their potential use in HIV-1 prevention. Results from non-human primate models using a cytomegalovirus vector have also shown the potential for a prophylactic HIV vaccine to induce effective T cell responses. Finally, the development of new vaccine vectors and trial strategies has also allowed progress in the field. Therefore, HIV-1 vaccine research remains a dynamic field that has also been stimulated by the recent positive results of pre-exposure prophylaxis strategies with antiretrovirals.

Published
2016
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17. Characterization of Physicians That Might Be Reluctant to Propose HIV Cure-Related Clinical Trials with Treatment Interruption to Their Patients? The ANRS-APSEC Study

Author

Christel Protiere, Lisa Fressard, Marion Mora, Laurence Meyer, Marie Préau, Marie Suzan-Monti, Jean-Daniel Lelièvre, Olivier Lambotte, Bruno Spire, and the APSEC Study Group

Subjects
HIV cure research, HIV cure-related clinical trials, physicians, viewpoints, analytical treatment interruption studies, principal component analysis, Medicine
Abstract

HIV cure-related clinical trials (HCRCT) with analytical antiretroviral treatment interruptions (ATIs) have become unavoidable. However, the limited benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians’ motivations to propose HCRCT to patients. Between October 2016 and March 2017, 164 French HIV physicians were asked about their level of agreement with four viewpoints regarding HCRCT. A reluctance score was derived from their answers and factors associated with reluctance identified. Results showed the highest reluctance to propose HCRCT was among physicians with a less research-orientated professional activity, those not informing themselves about cure trials through scientific literature, and those who participated in trials because their department head asked them. Physicians’ perceptions of the impact of HIV on their patients’ lives were also associated with their motivation to propose HCRCT: those who considered that living with HIV means living with a secret were more motivated, while those worrying about the negative impact on person living with HIV’s professional lives were more reluctant. Our study highlighted the need to design a HCRCT that minimizes constraints for participants and for continuous training programs to help physicians keep up-to-date with recent advances in HIV cure research.

Published
2020
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18. Negative modulation of suppressive HIV-specific regulatory T cells by IL-2 adjuvanted therapeutic vaccine.

Author

Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, and Nabila Seddiki

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40. IL-2 administration increased significantly HIV-specific CD4+CD25+CD134+ T-cell responses, which inversely correlated with viral load after TI (r = -0.7, p

Published
2017
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19. P2X7 Receptor Inhibition Improves CD34 T-Cell Differentiation in HIV-Infected Immunological Nonresponders on c-ART.

Author

Inna Menkova-Garnier, Hakim Hocini, Emile Foucat, Pascaline Tisserand, Laure Bourdery, Constance Delaugerre, Clarisse Benne, Yves Lévy, and Jean-Daniel Lelièvre

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Peripheral CD4+ T-cell levels are not fully restored in a significant proportion of HIV+ individuals displaying long-term viral suppression on c-ART. These immunological nonresponders (INRs) have a higher risk of developing AIDS and non-AIDS events and a lower life expectancy than the general population, but the underlying mechanisms are not fully understood. We used an in vitro system to analyze the T- and B-cell potential of CD34+ hematopoietic progenitor cells. Comparisons of INRs with matched HIV+ patients with high CD4+ T-cell counts (immune responders (IRs)) revealed an impairment of the generation of T-cell progenitors, but not of B-cell progenitors, in INRs. This impairment resulted in the presence of smaller numbers of recent thymic emigrants (RTE) in the blood and lower peripheral CD4+ T-cell counts. We investigated the molecular pathways involved in lymphopoiesis, focusing particularly on T-cell fate specification (Notch pathway), survival (IL7R-IL7 axis) and death (Fas, P2X7, CD39/CD73). P2X7 expression was abnormally strong and there was no CD73 mRNA in the CD34+ cells of INRs, highlighting a role for the ATP pathway. This was confirmed by the demonstration that in vitro inhibition of the P2X7-mediated pathway restored the T-cell potential of CD34+ cells from INRs. Moreover, transcriptomic analysis revealed major differences in cell survival and death pathways between CD34+ cells from INRs and those from IRs. These findings pave the way for the use of complementary immunotherapies, such as P2X7 antagonists, to restore T-cell lymphopoiesis in INRs.

Published
2016
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20. Gynoid Fat Distribution and Adipocyte Trapping May Explain Virological Failure With Intramuscular Long-Acting Cabotegravir and Rilpivirine

Author

Isabelle de Malliard, Anne-Laure Houist, Gilles Peytavin, Thomas L’Yavanc, Magali Bouvier, Pierre Cappy, Jean-Daniel Lelièvre, Elsa Feredj, William Vindrios, Sebastien Gallien, and Giovanna Melica

Subjects
Infectious Diseases, Oncology
Abstract

Intramuscular long-acting antiretroviral drugs can improve adherence to lifelong antiretroviral treatment. Nevertheless, adipose tissue thickness and distribution play a critical role with injectable drugs. We describe a virological failure with cabotegravir and rilpivirine in a Black African woman with human immunodeficiency virus type 1 with gynoid fat distribution (ie, adipose tissue prevailing in the pelvis and hip area) and body mass index

Published
2023

21. Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals

Author

Mathieu Hubert, Florence Guivel-Benhassine, Timothée Bruel, Françoise Porrot, Delphine Planas, Jessica Vanhomwegen, Aurélie Wiedemann, Sonia Burrel, Stéphane Marot, Romain Palich, Gentiane Monsel, Harouna Diombera, Sébastien Gallien, Jose Luis Lopez-Zaragoza, William Vindrios, Fabien Taieb, Sandrine Fernandes-Pellerin, Maurine Delhaye, Hélène Laude, Laurence Arowas, Marie-Noelle Ungeheuer, Laurent Hocqueloux, Valérie Pourcher, Thierry Prazuck, Anne-Geneviève Marcelin, Jean-Daniel Lelièvre, Christophe Batéjat, Yves Lévy, Jean-Claude Manuguerra, and Olivier Schwartz

Subjects
Virology, Parasitology, Microbiology
Published
2023

22. Profound Defect of Amphiregulin Secretion by Regulatory T Cells in the Gut of HIV-Treated Patients

Author

Mubashira Tariq, Sébastien Gallien, Mathieu Surenaud, Aurélie Wiedemann, Francette Jean-Louis, Christine Lacabaratz, José Luis Lopez Zaragoza, Jean-David Zeitoun, Saliha Ysmail-Dalhouk, Jean-Daniel Lelièvre, Yves Lévy, and Sophie Hüe

Subjects
CD4-Positive T-Lymphocytes, Inflammation, Gastrointestinal Diseases, Immunology, Humans, Immunology and Allergy, HIV Infections, Intestinal Mucosa, Interleukin-33, Amphiregulin, T-Lymphocytes, Regulatory
Abstract

The persistence of a leaky gut in HIV-treated patients leads to chronic inflammation with increased rates of cardiovascular, liver, kidney, and neurological diseases. Tissue regulatory T (tTreg) cells are involved in the maintenance of intestinal homeostasis and wound repair through the IL-33 pathway. In this study, we investigated whether the persistence of gut mucosal injury during HIV infection might be explained in part by a flaw in the mechanisms involved in tissue repair. We observed an increased level of IL-33 in the gut of HIV-infected patients, which is associated with an increased level of fibrosis and a low peripheral reconstitution of CD4+ T cells. Our results showed that intestinal Treg cells from HIV-infected patients were enriched in tTreg cells prone to support tissue repair. However, we observed a functional defect in tTreg cells caused by the lack of amphiregulin secretion, which could contribute to the maintenance of intestinal damage. Our data suggest a mechanism by which the lack of amphiregulin secretion by tTreg may contribute to the lack of repair of the epithelial barrier.

Published
2022

23. In-Depth Characterization of Full-Length Archived Viral Genomes after Nine Years of Posttreatment HIV Control

Author

Pauline Trémeaux, Frédéric Lemoine, Adeline Mélard, Marine Gousset, Faroudy Boufassa, Sylvie Orr, Valérie Monceaux, Olivier Gascuel, Olivier Lambotte, Laurent Hocqueloux, Asier Saez-Cirion, Christine Rouzioux, Véronique Avettand-Fenoel, Firouzé Bani-Sadr, Maxime Hentzien, Jean-Luc Berger, Isabelle Kmiec, Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Véronique Lambry, Anne-Cécile Beaudrey, Gilles Pialoux, Julie Chas, Christia Palacios, Anne Adda, Jean Paul Viard, Marie-Josée Dulucq, Laurence Weiss, Marina Karmochkine, Mohamed Meghadecha, Dominique Salmon-Ceron, Marie-Pierre Piétri, Philippe Blanche, Jean-Michel Molina, Olivier Taulera, Diane Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu Godinot, Valérie Artizzu, Patrick Miailhes, Laurent Cotte, Sophie Pailhes, Anne Conrad, Ludovic Karkowski, Stanislas Ogoudjobi, Yazdan Yazdanpanah, Sophie Matheron, Cindy Godard, Louis Bernard, Frédéric Bastides, Olivier Bourgault, Christine Jacomet, Emilie Goncalves, Pascal Chavanet, Lionel Piroth, Sandrine Gohier, Agnès Meybeck, Thomas Huleux, Pauline Cornavin, Yasmine Debab, David Théron, Thierry Prazuck, Barbara De Dieuleveult, Jean-Pierre Faller, Patricia Eglinger, Pascal Roblot, David Plainchamp, Hugues Aumaître, Martine Malet, Christine Rouger, Gérard Rémy, Melle Kmiec Isabelle, Jean-Luc Delassus, Alain Devidas, Eric Froguel, Sylvie Tassi, Philippe Genet, Juliette Gerbe, Olivier Patey, Richier Laurent, Marie-Christine Drobacheff, Aurélie Proust, Helder Gil, Laurence Gérard, Eric Oksenhendler, Caroline Lascoux, Sylvie Parlier, Frédéric Lucht, Véronique Ronat, Michel Dupon, Hervé Dutronc, Séverine Le Puil, Didier Neau, Patrick Mercié, Philippe Morlat, Sabrina Caldato, Jean-Luc Schmit, Nathalie Decaux, Jean-Pierre Bru, Gaëlle Clavere, Jean-François Delfraissy, Cécile Goujard, Katia Bourdic, Daniel Vittecoq, Claudine Bolliot, Thierry Lambert, Jean-François Bergmann, Maguy Parrinello, Yves Welker, Alain Lafeuillade, Gisèle Philip, Christophe Rapp, Melle Lerondel, Pierre de Truchis, Berthe Huguette, Vincent Jeantils, Fatouma Mchangama, Paul Henri Consigny, Fatima Touam, Sophie le Nagat, Olivier Bouchaud, Patricia Honoré, François Boué, Mariem Raho-Moussa, Jean-Paul Viard, Agnès Cros, Dominique Salmon-Céron, Marie-Pierre Pietri, Lio Collias, David Zucman, Olivier Blétry, Dominique Bornarel, Emmanuel Mortier, Zeng Feng, Jean-Daniel Lelièvre, Christine Katlama, Yasmine Dudoit, Anne Simon, Catherine Lupin, Pierre-Marie Girard, Michèle Pauchard, Sylvie Abel, André Cabié, Pascale Fialaire, Jean-Marie Chennebault, Sami Rehaiem, Luc de Saint Martin, •••• Perfezou, Jean-Charles Duthe, Pierre Weinbreck, Claire Genet, Florence Garnier, Isabelle Poizot-Martin, Olivia Fauche, Alena Ivanova, Patrick Philibert, Mame Penda Sow, Patrick Yeni, Cyndi Godard, François Raffi, Hervé Hüe, Philippe Perré, Pierre Marie Roger, Aline Joulie, Éric Rosenthal, Christian Michelet, Faouzi Souala, Maja Ratajczak, Marialuisa Partisani, Patricia Fischer, Pascale Nau, Pierre Delobel, Florence Balsarin, Marc De Lavaissiere, Renaud Verdon, Philippe Feret, Pascale Leclercq, •••• Gerberon, Agnés Meybeck, Raphaël Biekre, Thierry May, •••• Bouillon, François Caron, David Theron, Marc Gatfosse, Martin Martinot, Anne Pachart, Patrice Poubeau, Catherine Gaud, Agnès Uludag, Philippe Arsac, Lydia Bouaraba, Barbara de Dieulevault, Isabelle De Lacroix Szmania, Laurent Richier, Vincent Daneluzzi, Elisabeth Rouveix, Geneviève Beck-Wirth, Philippe Romand, Laurent Blum, Martine Deschaud, Christophe Michau, Christian Bernard, Florence Salaun, Philippe Muller, Yves Poinsignon, Annie Lepretre, Albert Sotto, •••• Doncesco, Pascale Perfezou, Jean Charles Duthe, Mathilde Aurore Niault, Virginie Mouton-Rioux, Jean-Philippe Talarmin, Jean Charles Duthé, Mathilde Dupont, Stéphane Natur, Hikombo Hitoto, and Ali Mahamadou Ibrahim

Subjects
Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, Ecology, Physiology, Genetics, Cell Biology
Abstract

Most people living with HIV need antiretroviral therapy to control their infection and experience viral relapse in case of treatment interruption, because of viral reservoir (proviruses) persistence. Knowing that proviruses are very diverse and most of them are defective in treated individuals, we aimed to characterize the HIV blood reservoirs of posttreatment controllers (PTCs), rare models of drug-free remission, in comparison with spontaneous controllers and treated individuals.

Published
2023

24. Research priorities to increase vaccination coverage in Europe (EU joint action on vaccination)

Author

Sándor Bozóki, Jean-Daniel Lelièvre, András Micsik, Marie Paule Kieny, Florence Francis-Oliviero, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Biomedical Research, COVID-19 Vaccines, Vaccination Coverage, Context (language use), Task (project management), 03 medical and health sciences, 0302 clinical medicine, Multi-criteria decision analysis, Health care, Humans, 030212 general & internal medicine, Child, Research question, Research priorities, General Veterinary, General Immunology and Microbiology, Health Priorities, SARS-CoV-2, business.industry, 030503 health policy & services, Vaccination, Public Health, Environmental and Occupational Health, Equity (finance), COVID-19, Public relations, Multiple-criteria decision analysis, 3. Good health, Europe, Infectious Diseases, Influenza Vaccines, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, business, Decision analysis
Abstract

Background Deciding how best to invest in healthcare is never an easy task and prioritization is therefore an area of great interest for policymakers. Too low public vaccine confidence, which results in insufficient vaccine uptake, remains an area of concern for EU policy-makers. Within the European Joint action on vaccination, a work-package dedicated to research aims to define tools and methods for priority-setting in the field of vaccination research. We therefore propose a prioritization framework to identify research priorities towards generating and synthesizing evidence to support policies and strategies aiming at increasing vaccine coverage. Materials/methods We used a multi-criteria decision analysis (MCDA) method inspired by the Child Health and Nutrition Research Initiative developed by Rudan et al. This quantitative methodology follows a series of steps involving different groups of experts and relevant stakeholders. The first step consists in identifying key research questions through a broad consultation. In parallel, a first group of experts is tasked to select criteria for prioritization of research questions, taking into consideration the ultimate goal of the exercise. Another group of experts is then requested to assess a weight to each of the criteria, using pair-wise comparisons. The final step consists in gathering experts who will assess each research question against the weighted criteria. This evaluation leads to assigning a score to each individual research question, which can then be ranked in order of priority. Results We focused our work on four pre-selected pilot vaccines (pertussis, measles containing combination vaccines, influenza and HPV). The consultation generated 124 questions, which were secondarily sorted and re-worded to obtain 27 questions to be ranked. Criteria for setting priorities were the following: accessibility, answerability, deliverability, disease prevalence/incidence, effectiveness, equity, generalization, and territory. During a final face-to-face meeting international experts ranked the 27 questions and agreed on a consensual list of six top-priorities. Conclusions We have developed a transparent, evidence-based rigorous framework to defined key research questions to generate evidence towards the design of policies and strategies to increase vaccine coverage. Results were disseminated broadly and submitted to the EC for potential funding in the context of The Horizon Europe Program. The same process will be conducted in 2021 to identify vaccination research priorities regarding all vaccines used in the EU as well as COVID-19 vaccines.

Published
2021

25. 84. One-month Humoral Response Following Two Doses of Covid-19 Vaccines in Specific populations – ANRS0001S COV POPART Cohort Study

Author

Paul LOUBET, L I nda Wittkop, Mathieu Chalouni, David-Axel Laplaud, Martine Laville, Bruno Laviolle, Jean-Daniel Lelièvre, Jean-Yves Blay, Benoit Barrou, Benjamin Terrier, Laure Esterle, Stephanie Nguyen, Axel Levier, Eric Tartour, Xavier de Lamballerie, and Odile Launay

Subjects
Infectious Diseases, Oncology
Abstract

Background We evaluated the immune response to COVID-19 vaccines in several specific populations at high risk of severe COVID-19. Methods Participants from the French national multi-center prospective cohort study ANRS0001S COV-POPART were included (11 specific subpopulations: and 2 control groups (18–64 years and over 65 years)). In this preliminary analysis patients and controls who had received at least two vaccine doses have been included. Percentages (95% confidence intervals (CI)) of participants with anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were evaluated at one month after the second dose of COVID-19 vaccine. Results 3703 were included: 2650 participants from specific subpopulations (171 solid cancers, 160 SOT, 100 HCT, 91 chronic renal failures, 141 systemic autoimmune diseases, 157 autoimmune inflammatory rheumatic diseases, 361 multiple sclerosis (MS) or neuromyelitis optica spectrum disorders, 61 hypogammaglobulinemia, 401 diabetic, 739 obeses non-diabetic and 476 HIV) and 1053 controls (893: 18–64 years and 160 over 65 years). Median age was 51.7 years [InterQuartile range: 40.8 – 60.9] and 50.7% were male. Most of the participants received BNT162b2 vaccine (86.4%). In the control group, 100% (95%CI: 99.6;100.0) of those aged 18–64 and 99.4% (96.6; 100.0) of those over 65 years developed anti-Spike IgG antibodies. PLWHIV, cancer and diabetic patients had high rate of responders after two doses with 98.3% (97.2;99.1), 93.0% (88.1;96.3) and 92.0% (88.9;94.5), respectively. The lowest percentage of responders was found in patients with SOT (13.8% (8.8;20.1), HSCT (34.0% (24.8;44.2) and hypogammaglobulinemia (52.5% 39.3;65.4). In both control groups, the frequency of neutralizing antibodies was similar to the anti-Spike IgG antibody response. In the immunodeficient populations, neutralizing antibodies responders tended to be less frequent than anti-Spike antibodies responders. Similar trends than for IgG antibody were identified (Figure 1). Anti-Spike and Neutralizing antibody (Ab) responses (95% CI) one month after the second dose of COVID-19 vaccine in specific and control populations. Conclusion Lower COVID-19 vaccine humoral response was observed in specific populations than in controls, especially in patients with hypogammaglobulinemia, HSCT and SOT. Disclosures Paul LOUBET, MD, PhD, pfizer: Board Member Odile Launay, MD, PhD, AstraZeneca: Financial|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Grant/Research Support|MD: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Data safety monitoring board|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data safety monitoring board.

Published
2022

26. A comparison of Sars-Cov-2 vaccine platforms: the CoviCompare project

Author

Diana Molino, Christine Durier, Anne Radenne, Corinne Desaint, Jacques Ropers, Soizic Courcier, Louis Victorien Vieillard, Claire Rekacewicz, Beatrice Parfait, Victor Appay, Frédéric Batteux, Emmanuel Barillot, Michel Cogné, Béhazine Combadière, Christiane S. Eberhardt, Guy Gorochov, Philippe Hupé, Laetitia Ninove, Stéphane Paul, Isabelle Pellegrin, Sylvie van der Werf, Maeva Lefebvre, Elisabeth Botelho-Nevers, Inmaculada Ortega-Perez, Marie Jaspard, Samba Sow, Jean Daniel Lelièvre, Xavier de Lamballerie, Marie Paule Kieny, Eric Tartour, Odile Launay, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Faculté de médecine [Genève], Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD), Physiologie cellulaire des régulations hormonale, nutritionnelles et pharmacologiques (UMR-S-530), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Alliance for International medical Action (ALIMA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre pour le Développement des Vaccins [Mali], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biochimie des Lipides, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Ministere des Solidarites et de la Sante, Ministere de l'Enseignement Superieur, de la Recherche et de l'Innovation, Coalition for Epidemic Preparedness Innovations (CEPI), ANRS \Emerging Infectious Diseases, ANR-20-COV3-0004,CoMemRep,Caractérisation des complexes de réplication associés à la membrane du SARS CoV 2(2020), Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Chard-Hutchinson, Xavier, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
[SDV] Life Sciences [q-bio], COVID-19 Vaccines, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, SARS-CoV-2, [SDV]Life Sciences [q-bio], Spike Glycoprotein, Coronavirus, COVID-19, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, General Biochemistry, Genetics and Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2022

27. Belatacept-based immunosuppressive regimen in HIV-positive kidney transplant recipients

Author

Karim El Sakhawi, Philippe Attias, Anissa Moktefi, Alexandre Ingels, Philippe Remy, Dominique Bertrand, Marie Matignon, C. Champy, Giovanna Melica, Cyril Garrouste, Anne Scemla, David Mokrani, David Kheav, Antoine Morel, Philippe Grimbert, Paolo Malvezzi, and Jean-Daniel Lelièvre

Subjects
medicine.medical_specialty, medicine.medical_treatment, Population, 030232 urology & nephrology, graft survival, kidney transplantation, 030230 surgery, Belatacept, acute rejection, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Adverse effect, education, AcademicSubjects/MED00340, Kidney transplantation, Transplantation, education.field_of_study, immunosuppression, business.industry, graft function, Immunosuppression, Original Articles, medicine.disease, Calcineurin, Nephrology, Cohort, business, medicine.drug
Abstract

Background Kidney allograft survival in human immunodeficiency virus (HIV)-positive patients is lower than that in the general population. Belatacept increases long-term patient and allograft survival rates when compared with calcineurin inhibitors (CNIs). Its use in HIV-positive recipients remains poorly documented. Methods We retrospectively report a French cohort of HIV-positive kidney allograft recipients who were switched from CNI to belatacept, between June 2012 and December 2018. Patient and allograft survival rates, HIV immunovirological and clinical outcomes, acute rejection, opportunistic infections (OIs) and HLA donor-specific antibodies (DSAs) were analysed at 3 and 12 months, and at the end of follow-up (last clinical visit attended after transplantation). Results were compared with HIV-positive recipients group treated with CNI. Results Twelve patients were switched to belatacept 10 (2–25) months after transplantation. One year after belatacept therapy, patient and allograft survival rates scored 92% for both, two (17%) HIV virological rebounds occurred due to antiretroviral therapy non-compliance, and CD4+ and CD8+ T-cell counts remained stable over time. Serious adverse events included two (17%) acute steroid-resistant T-cell-mediated rejections and three (25%) OIs. Kidney allograft function significantly increased over the 12 post-switch months (P = 0.009), and DSAs remained stable at 12 months after treatment. The control group showed similar results in terms of patient and kidney allograft survival rates, DSA characteristics and proteinuria Conclusions Switch from CNI to belatacept can be considered safe and may increase long-term kidney allograft survival in HIV-positive kidney allograft recipients. These results need to be confirmed in a larger cohort.

Published
2020

28. Single-cell RNA-Seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells

Author

Flavien Brouiller, Francesca Nadalin, Ouardia Aït Mohamed, Pierre-Emmanuel Bonté, Constance Delaugerre, Jean-Daniel Lelièvre, Florent Ginhoux, Nicolas Ruffin, and Philippe Benaroch

Abstract

Sensing of incoming viruses represents one of the pivotal tasks of dendritic cells (DC). Human primary blood DC encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of Axl+DC, a new blood DC subset, endowed with unique capacities to bind, replicate, and transmit HIV-1 prompted us to evaluate its anti-viral response. We show that HIV-1 induced two main broad and intense transcriptional programs in different Axl+DC potentially induced by different sensors; a NF-κB-mediated program that led to DC maturation and efficient antigen-specific CD4+T cell activation, and a program mediated by STAT1/2 that activated type I IFN and an ISG response. These responses were absent from cDC2 exposed to HIV-1 except when viral replication occurred. Finally, Axl+DC actively replicating HIV-1 identified by quantification of viral transcripts exhibited a mixed NF-κB/ISG innate response. Our results suggest that the route of HIV-1 entry may dictate different innate sensing pathway by DC.

Published
2022

29. Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection

Author

Joanne Byrne, Lili Gu, Alejandro Garcia-Leon, Colette Marie Gaillard, Gurvin Saini, Dana Alalwan, Julen Tomás-Cortázar, Grace Kenny, Sean Donohue, Bearach Reynolds, Tessa O’Gorman, Alan Landay, Peter Doran, Jannik Stemler, Philipp Koehler, Rebecca Jane Cox, Ole F. Olesen, Jean-Daniel Lelievre, Cathal O’Broin, Stefano Savinelli, Eoin R. Feeney, Jane A. O’Halloran, Aoife Cotter, Mary Horgan, Christine Kelly, Corrina Sadlier, Eoghan de Barra, Oliver A. Cornely, Virginie Gautier, Patrick WG Mallon, All Ireland Infectious Diseases cohort study and VACCELERATE consortium, A. Cotter, E. Muldoon, G. Sheehan, T. McGinty, J. S. Lambert, T. O’Gorman, C. Kelly, K. Leamy, J. Byrne, G. Kenny, K. McCann, R. McCann, C. O’Broin, S. Savinelli, J. O’Halloran, E. Feeney, P. W. G. Mallon, A. Garcia Leon, S. Miles, D. Alalwan, R. Negi, G. Saini, E. Moore, E. de Barra, S. McConkey, K. Hurley, B. Jacob, F. Lyons, M. Horgan, C. Sadlier, T. Bracken, B. Whelan, J Low, O Yousif, B. McNicholas, G. Courtney, C. O’Maoldomhnaigh, P. Gavin, Julia M. Neuhann, Ullrich Bethe, Sarah Heringer, Jon Salmanton-Garcı́a, Lea Tischmann, Arnd Cüppers, Jan Grothe, Antonio J. Carcas, Jesús Frías-Iniesta, Murat Akova, Alejandro Garcia Leon, Patrick Mallon, Riya Negi, Colette Gaillard, Christine Lammens, An Hotterbeekx, Katherine Loens, Surbhi Malhotra-Kumar, Herman Goossens, Samir Kumar-Singh, Franz König, Lusine Yeghiazaryan, and Martin Posch

Subjects
SARS-CoV-2, COVID-19, COVID-19 vaccine, immunogenicity, B cells, T cells, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionA clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection.MethodsAdults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti–SARS-CoV-2 receptor-binding domain (RBD) and spike-subunit-1 and spike-subunit-2 antibodies were measured. A sub-study assessed SARS-CoV-2–specific plasma and memory B-cell and memory T-cell responses in peripheral blood mononuclear cells by enzyme-linked immunospot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan–Meier survival analysis, and Cox proportional hazard ratios.ResultsOf the 132 participants, 47 (36%) reported incident SARS-CoV-2 infection at a median 16.5 (16.25–21) weeks after the third-dose vaccination. RBD titres and B-cell responses, but not T-cell responses, increased after the third-dose vaccine. Whereas no significant difference in day 14 antibody titres or T-cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B-cell frequencies were significantly higher in those who did not develop infection [10.0% (4.5%–16.0%) versus 4.9% (1.6%–9.3%), p = 0.01]. RBD titres and memory B-cell frequencies remained significantly higher at 10 months than day 0 levels (p < 0.01).DiscussionRobust antibody and B-cell responses persisted at 10 months following the third-dose vaccination. Higher memory B-cell frequencies, rather than antibody titres or T-cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection.

Published
2024
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30. Humoral response after mRNA COVID-19 primary vaccination and single booster dose in people living with HIV compared to controls: A French nationwide multicenter cohort study—ANRS0001s COV-POPART

Author

Paul Loubet, Jean-Daniel Lelievre, Alexis François, Elisabeth Botelho-Nevers, Christian Chidiac, David Chirio, Vincent Dubee, Bertrand Dussol, Florence Galtier, Mojgan Hessamfar, Enkelejda Hodaj, Sylvain Jaffuel, Karine Lacombe, Fabrice Laine, Maeva Lefebvre, Zoha Maakaroun-Vermesse, Alain Makinson, Aurelie Portefaix, Valerie Pourcher, David Rey, David Zucman, Julie Longobardi, Mathilde Bertheau, Eric Tartour, Xavier de Lamballerie, Odile Launay, and Linda Wittkop

Subjects
SARS-CoV-2, Vaccines, HIV, Immunogenicity, COVID-19, Infectious and parasitic diseases, RC109-216
Abstract

Background: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals. Methods: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (

Published
2024
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31. Cytokine profile of anti-spike CD4+T cells predicts humoral and CD8+T cell responses after anti-SARS-CoV-2 mRNA vaccination

Author

Nadine Benhamouda, Anissa Besbes, Rebecca Bauer, Nesrine Mabrouk, Gauthier Gadouas, Corinne Desaint, Lucie Chevrier, Maeva Lefebvre, Anne Radenne, Marie Roelens, Béatrice Parfait, Daniela Weiskopf, Alessandro Sette, Nadège Gruel, Marie Courbebaisse, Victor Appay, Stephane Paul, Guy Gorochov, Jacques Ropers, Said Lebbah, Jean-Daniel Lelievre, Ludger Johannes, Jonathan Ulmer, David Lebeaux, Gerard Friedlander, Xavier De Lamballerie, Patrice Ravel, Marie Paule Kieny, Fréderic Batteux, Christine Durier, Odile Launay, and Eric Tartour

Subjects
Health sciences, Immunity, Virology, Mathematical biosciences, Machine learning, Science
Abstract

Summary: Coordinating immune responses – humoral and cellular – is vital for protection against severe Covid-19. Our study evaluates a multicytokine CD4+T cell signature’s predictive for post-vaccinal serological and CD8+T cell responses. A cytokine signature composed of four cytokines (IL-2, TNF-α, IP10, IL-9) excluding IFN-γ, and generated through machine learning, effectively predicted the CD8+T cell response following mRNA-1273 or BNT162b2 vaccine administration. Its applicability extends to murine vaccination models, encompassing diverse immunization routes (such as intranasal) and vaccine platforms (including adjuvanted proteins). Notably, we found correlation between CD4+T lymphocyte-produced IL-21 and the humoral response. Consequently, we propose a test that offers a rapid overview of integrated immune responses. This approach holds particular relevance for scenarios involving immunocompromised patients because they often have low cell counts (lymphopenia) or pandemics. This study also underscores the pivotal role of CD4+T cells during a vaccine response and highlights their value in vaccine immunomonitoring.

Published
2024
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32. A French cohort for assessing COVID-19 vaccine responses in specific populations

Author

Benoit Barrou, David-Axel Laplaud, Odile Launay, Stéphanie Nguyen, Jean-Daniel Lelièvre, Jean-Yves Blay, Benjamin Terrier, Martine Laville, Anne Thiebaut, Jacques Morel, Xavier de Lamballerie, Béatrice Parfait, Bruno Laviolle, Jean-François Viallard, Linda Wittkop, François Vrtovsnik, Jean-Philippe Spano, Paul Loubet, Maryvonne Hourmant, Marie Lachâtre, Eric Tartour, Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Association Francaise d'Etudes et de Recherches sur l'Obesite, Partenaires INRAE, Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS00001S, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], Université de Bordeaux (UB), Université de Paris (UP), Institut de Recherche pour le Développement (IRD), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Virulence Bactérienne et Infections Chroniques (VBIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Grenoble, Université Paris Diderot - Paris 7 (UPD7), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Adolescent, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Immunocompromised Host, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Young adult, ComputingMilieux_MISCELLANEOUS, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, COVID-19, General Medicine, Middle Aged, Antibodies, Neutralizing, Virology, 3. Good health, Viral infection, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract

International audience; No abstract available

Published
2021

33. An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years

Author

Mickaël Alligon, Nizar Mahlaoui, Virginie Courteille, Laurence Costes, Veronica Afonso, Philippe Randrianomenjanahary, Nathalie de Vergnes, Anja Ranohavimparany, Duy Vo, Inès Hafsa, Perrine Bach, Vincent Benoit, Nicolas Garcelon, Alain Fischer, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Corinne Armari-Alla, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, David Boutboul, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Martin Castelle, Pascal Cathebras, Emilie Catherinot, Nathalie Cheikh, Morgane Cheminant, Sarah Cohen-Beaussant, Thibault Comont, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Lionel Crevon, Elisa Demonchy, Anne Deville, Catherine Devoldere, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz-Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaëlle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Jean-Philippe Jais, Sarah Jannier, Serge Jacquot, Roland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, David Launay, Emmanuelle Le Moigne, Alain Le Quellec, Vincent Le Moing, Yvon Lebranchu, Marc Lecuit, Guillaume Lefèvre, Jean-Daniel Lelièvre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Luminita Luca, Coralie Mallebranche, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin-Silva, Agathe Masseau, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Charline Miot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Münzer, Robert Navarro, Bénédicte Neven, Dalila Nouar, Raphaële Nove-Josserand, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Sophie Rivière, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Harry Sokol, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, and Jean-François Viallard

Subjects
Inflammation, Neoplasms, Immunology, Hypersensitivity, Immunologic Deficiency Syndromes, Immunology and Allergy, Humans, Autoimmunity, Retrospective Studies
Abstract

Noninfectious manifestations-allergy, autoimmunity/inflammation, lymphoproliferation, and malignancies-are known to exist in many primary immunodeficiency diseases (PID) and to participate in prognosis.To obtain a global view on their occurrence, we retrieved data from a retrospective cohort of 1375 patients included in the French National Reference Center for Primary Immune Deficiencies (CEREDIH) for whom we had a 10-year follow-up since inclusion in the registry.These patients were followed for 10 years (2009-2018) by specialized centers in university hospitals. This study showed that 20.1% of patients without prior curative therapy (n = 1163) developed at least 1 manifestation (event) encompassing 277 events.Autoimmune/inflammatory events (n = 138) and malignancies (n = 85) affected all age classes and virtually all PID diagnostic groups. They were associated with a risk of death that occurred in 195 patients (14.2%) and were found to be causal in 43% of cases. Malignancies (odds ratio, 5.62; 95% confidence interval, 3.66-8.62) and autoimmunity (odds ratio, 1.9; 95% confidence interval, 1.27-2.84) were clearly identified as risk factors for lethality. Patients who underwent curative therapy (mostly allogeneic hematopoietic stem cell transplantation, with a few cases of gene therapy or thymus transplantation) before the 10-year study period (n = 212) had comparatively reduced but still detectable clinical manifestations (n = 16) leading to death in 9.4% of them.This study points to the frequency and severity of noninfectious manifestations in various PID groups across all age groups. These results warrant further prospective analysis to better assess their consequences and to adapt therapy, notably indication of curative therapy.

Published
2021

34. Les vaccins de demain

Author

Jean-Daniel Lelièvre

Subjects
Vaccine research, Computer science, Biochemistry (medical), Reverse vaccinology, Context (language use), Computational biology, 030204 cardiovascular system & hematology, Analytical Chemistry, Viral vector, DNA vaccination, Vaccination, 03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis
Abstract

Vaccination represents one of the major advances in the field of health. The first vaccines were produced on a rather empirical concept based on the so-called 3I strategy: isolation, inactivation, injection. More recently, protein vaccines have emerged. However, the emergence of new pathogens, the inefficiency of these vaccine strategies to protect against several infections, the need to be able to develop new vaccines quickly and at low cost have led to the development of new types of vaccines. In this context vaccines based on the use of the nucleic acid coding sequences of the antigens of interest (viral vectors, DNA vaccines, RNA vaccines) have been developed in order to improve the efficiency of the currently available vaccines and to propose generic platforms potentially usable against a large number of different pathogens. In addition to the use of these new vaccines, ongoing vaccine research is benefiting from technological developments aimed at optimally delivering vaccines, targeting, for example, dendritic cells, and better characterizing the antigens of interest through the use of vaccines of reverse vaccinology.

Published
2019

35. Interview With Jean-Daniel Lelièvre, PU-PH, Head of the Research Clinic of the VRI (Vaccine Research Institute)

Author

Caroline Ollivier-Yaniv and Jean-Daniel Lelièvre

Subjects
0301 basic medicine, Vaccine research, medicine.medical_specialty, business.industry, Head (linguistics), 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, Family medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, business
Published
2018

36. Viral genomic, metagenomic and human transcriptomic characterization and prediction of the clinical forms of COVID-19

Author

Slim Fourati, Elisabeth Trawinski, Olivier Langeron, Paul-Louis Woerther, Melissa N'Debi, William Vindrios, G. Gricourt, Nicolas de Prost, Jean-Daniel Lelièvre, Raphaël Lepeule, Christophe Rodriguez, Claudie Lamoureux, Oriane Picard, Isaac Désveaux, Vanessa Démontant, Laure Surgers, Florence Canoui-Poitrine, Nicolas Mongardon, Armand Mekontso-Dessap, Jean-Michel Pawlotsky, and José L. Cohen

Subjects
0301 basic medicine, Male, RNA viruses, Viral Diseases, Pulmonology, Coronaviruses, Disease, Biochemistry, Receptors, Interleukin-8B, law.invention, 0302 clinical medicine, Medical Conditions, law, Outpatients, Medicine and Health Sciences, Medicine, Respiratory system, Biology (General), Pathology and laboratory medicine, Aged, 80 and over, Mortality rate, Genomics, Middle Aged, Medical microbiology, Intensive care unit, Pathophysiology, Bacterial Pathogens, Infectious Diseases, 030220 oncology & carcinogenesis, Viruses, Female, SARS CoV 2, Pathogens, Transcriptome Analysis, Research Article, Adult, Patients, SARS coronavirus, QH301-705.5, Immunology, Genome, Viral, Microbiology, 03 medical and health sciences, Respiratory Disorders, Immune system, Virology, Intensive care, Genetics, Humans, Molecular Biology, Aged, Biology and life sciences, business.industry, SARS-CoV-2, Organisms, Viral pathogens, COVID-19, Computational Biology, Covid 19, Th1 Cells, RC581-607, medicine.disease, Genome Analysis, Microbial pathogens, Health Care, Pneumonia, 030104 developmental biology, Respiratory Infections, Th17 Cells, Parasitology, Metagenomics, Immunologic diseases. Allergy, business, Transcriptome, Biomarkers
Abstract

COVID-19 is characterized by respiratory symptoms of various severities, ranging from mild upper respiratory signs to acute respiratory failure/acute respiratory distress syndrome associated with a high mortality rate. However, the pathophysiology of the disease is largely unknown. Shotgun metagenomics from nasopharyngeal swabs were used to characterize the genomic, metagenomic and transcriptomic features of patients from the first pandemic wave with various forms of COVID-19, including outpatients, patients hospitalized not requiring intensive care, and patients in the intensive care unit, to identify viral and/or host factors associated with the most severe forms of the disease. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. Severe pneumonia was associated with overexpression of cytokine transcripts activating the CXCR2 pathway, whereas patients with benign disease presented with a T helper “Th1-Th17” profile. The latter profile was associated with female gender and a lower mortality rate. Our findings indicate that the most severe cases of COVID-19 are characterized by the presence of overactive immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage. These findings make CXCR2 antagonists, in particular IL-8 antagonists, promising candidates for the treatment of patients with severe COVID-19., Author summary This study was the first to use shotgun metagenomics and in-depth bioanalysis of metagenomics data to understand the role of viral genomics, microorganism metagenomics and host transcriptomics in the severity of COVID-19. The study was performed using nasopharyngeal swabs collected from 104 patients with various severities of COVID-19 at the time of diagnosis. Neither the genetic characteristics of SARS-CoV-2, nor the detection of bacteria, viruses, fungi or parasites were associated with the severity of pulmonary disease. In contrast, host transcriptomic analyses showed that severe COVID-19 pneumonia is associated with overexpression of cytokine transcripts that activate the CXCR2 receptor pathway, whereas patients with benign disease present with a T helper “Th1-Th17” profile. The latter profile was associated with female gender and a lower mortality rate. These findings indicate that the most severe cases of COVID-19 are caused by excess neutrophil infiltration that enhances the inflammatory response and prolongs tissue damage. They suggest that CXCR2 antagonists, in particular IL-8 antagonists, could be promising candidates for the treatment of patients with severe COVID-19.

Published
2021

37. A randomized placebo-controlled efficacy study of a prime boost therapeutic vaccination strategy in HIV-1 infected individuals: VRI02 ANRS 149 LIGHT Phase II trial

Author

P.-M. Girard, L. Guillaumat, Emile Foucat, Valérie Boilet, Giuseppe Pantaleo, Aurélie Wiedemann, Yves Levy, L. Hocqueloux, Jean-Michel Molina, Laura Richert, E. Lhomme, Craig Fenwick, P. Morlat, Véronique Rieux, Jean-Daniel Lelièvre, Christine Lacabaratz, Olivier Bouchaud, C. Bauduin, Mathieu Surenaud, Rodolphe Thiébaut, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Admin, Oskar, Hôpital Albert Chenevier, Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Team MORPH3EUS (INSERM U1219 - UB - ISPED), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), University of Lausanne (UNIL), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and DARMIGNY, SANDRINE

Subjects
CD4-Positive T-Lymphocytes, Male, Antiretroviral therapy interruption, [SDV]Life Sciences [q-bio], HIV Infections, CD8-Positive T-Lymphocytes, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Vaccines, DNA, 030212 general & internal medicine, AIDS Vaccines, 0303 health sciences, human immunodeficiency virus, Immunogenicity, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Vaccination, Anti-Retroviral Agents, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.drug, Interleukin 2, Adult, Immunology, Immunization, Secondary, Viremia, Biology, Placebo, Microbiology, complex mixtures, 03 medical and health sciences, Immune system, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Virology, Vaccines and Antiviral Agents, medicine, Humans, 030304 developmental biology, clinical trials, HIV, medicine.disease, Therapeutic vaccine, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Insect Science, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, CD8
Abstract

In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually., In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P

Published
2021

38. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author

Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman

Subjects
COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Published
2024
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39. Factors Associated With Being Overweight and Obesity in People Living With Human Immunodeficiency Virus on Antiretroviral Therapy: Socioclinical, Inflammation, and Metabolic Markers

Author

P Hochedez, B Fantin, J Delgado, P M Girard, J Pavie, M P Bouillon, Jean-Philippe Bastard, Mathilde Ghislain, L Bernard, J Lamarque, O Lambotte, A Rami, Jeanne Goupil de Bouillé, Rodolphe Thiébaut, Jean-Paul Viard, Rosemary Dray-Spira, C Bazin, M André, L Weiss, F Z Makhoukhi, Alain-Serge Keita, Ventzislava Petrov-Sanchez, Delcey, A Villemant, A Richard, S Ogoudjobi, Tatiana Feitoza, C Lascoux-Combe, M Delestan, B Roze, Laurent Tran, David Rey, M Kassim, J Chas, B Lefebvre, Faroudy Boufassa, S Gibert, M J Carmantrand, L Gérard, G Blaison, L Slama, Claudine Duvivier, Philippe Morlat, S Parlier, A Ameur, L Meddeb, Cécile Goujard, S Matheron, Rémonie Seng, C Blanco Bétancourt, A Maignan, Isabelle Poizot-Martin, Z Ouazene, Sophie Abgrall, Yazdan Yazdanpanah, A Proust, Lorraine Plessis, André Cabié, M Guignard, S Pierre-François, C Crisol, Dominique Salmon, A Simon, S Caldato, Abdellatif Essabbani, D Beniken, P Perré, M C Marien, P Passe-Courtin, H Hue, Christian Chidiac, Corinne Vigouroux, L Traore, M Parrinello, A Benmammar, I Kansau, Catherine Chirouze, F Touam, S Poirier, C Chesnel, F Boué, Jean-Daniel Lelièvre, Jean-Paul Teglas, C Cerland, A Ivanova, J Zelie, M C Thiebaut-Drobacheff, J F Bergmann, Christine Rouzioux, T May, Laurence Meyer, S Lariven, M Martinot, M C Hallouin-Bernard, A Meybeck, D Makhloufi, M P Pietri, A Pachard, L Larmetand, Olivier Lortholary, M L Batard and, J P Viard, Dorothée Vignes, M Manea, M Mohseni Zadeh, F Louni, P Fischer, J Moreau, Jacques Reynes, Q Gardiennet, Olivier Bouchaud, C Tramoni, Joly, François Raffi, A S Batalla, D Neau, Robert Carlier, P Sellier, C Rioux, Laurent Cotte, K Bourdic, S Le Puil, A Pegeot, J M Molina, S Abel, O Bourgault, G H Tarnier-Cochin, M J Dulucq, Gilles Pialoux, F Ronin, Lucie Marchand, and Soraya Fellahi

Subjects
0301 basic medicine, Cart, Male, 030106 microbiology, Physiology, HIV Infections, Overweight, Weight Gain, 03 medical and health sciences, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, Obesity, Inflammation, Adiponectin, medicine.diagnostic_test, business.industry, medicine.disease, Infectious Diseases, Female, medicine.symptom, business, Lipid profile, Body mass index, Viral load, Weight gain
Abstract

Background We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). Methods Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5–24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, Results After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21–23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. Conclusion Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

Published
2020

40. TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice

Author

Sandra Zurawski, Hugo Mouquet, Craig Fenwick, Lishan Su, Laurine Gil, Giuseppe Pantaleo, Gerard Zurawski, Jean-Daniel Lelièvre, Mireille Centlivre, Pierre Milpied, Véronique Godot, Liang Cheng, Inaki Cervera-Marzal, Yves Levy, Colas Tcherakian, Guangming Li, Sylvain Cardinaud, and Nicolas Ortonne

Subjects
RNA viruses, B Cells, Physiology, medicine.medical_treatment, T-Lymphocytes, HIV Infections, HIV Antibodies, Pathology and Laboratory Medicine, Biochemistry, White Blood Cells, Mice, 0302 clinical medicine, Immunodeficiency Viruses, Animal Cells, Immune Physiology, Public and Occupational Health, Biology (General), AIDS Vaccines, 0303 health sciences, Vaccines, B-Lymphocytes, Immune System Proteins, Recombinant Vaccines, biology, Vaccination, env Gene Products, Human Immunodeficiency Virus, Vaccination and Immunization, Haematopoiesis, medicine.anatomical_structure, Medical Microbiology, 030220 oncology & carcinogenesis, Viral Pathogens, Viruses, Infectious diseases, Antibody, Stem cell, Cellular Types, Pathogens, Adjuvant, Research Article, Medical conditions, QH301-705.5, Immune Cells, Immunology, Somatic hypermutation, Spleen, Microbiology, Antibodies, 03 medical and health sciences, Virology, Infectious disease control, Vaccine Development, Retroviruses, Genetics, medicine, Animals, Humans, CD40 Antigens, Antibody-Producing Cells, Molecular Biology, Microbial Pathogens, 030304 developmental biology, Medicine and health sciences, CD40, Blood Cells, Biology and life sciences, Viral vaccines, Lentivirus, HIV vaccines, Organisms, HIV, Proteins, Cell Biology, RC581-607, Hematopoietic Stem Cells, Antibodies, Neutralizing, Immunoglobulin G, Toll-Like Receptor 9, biology.protein, HIV-1, Parasitology, Preventive Medicine, Immunologic diseases. Allergy
Abstract

The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans., Author summary Mice reconstituted with human hematopoietic stem cells (hu-mice) are a powerful tool for the study of human immune function in vivo and can be useful as a pre-clinical model to rank vaccination strategies. However, in hu-mice, human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. One finding of our study is that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mouse models. We further reported that the HIV-1 envelope-specific IgG+ hu-B cells elicited in hu-mice by the anti-CD40.Env vaccine used more VH3 and VH4 family genes and displayed higher rates of somatic hypermutations than the non-specific IgG+ hu-B-cell counterpart. VH3 antibodies are essential for antiviral immunity. We also showed that monitoring ICOS+ circulating Tfh cells seven days after the last booster immunization is a surrogate marker for vaccine-induced HIV-1-specific B-cell responses. Overall, we report important results, both in the setting of this hu-mouse model and for a prophylactic HIV vaccine.

Published
2020

41. Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time

Author

Grace Kenny, Sophie O’Reilly, Neil Wrigley Kelly, Riya Negi, Colette Gaillard, Dana Alalwan, Gurvin Saini, Tamara Alrawahneh, Nathan Francois, Matthew Angeliadis, Alejandro Abner Garcia Leon, Willard Tinago, Eoin R. Feeney, Aoife G. Cotter, Eoghan de Barra, Obada Yousif, Mary Horgan, Peter Doran, Jannik Stemler, Philipp Koehler, Rebecca Jane Cox, Donal O’Shea, Ole F. Olesen, Alan Landay, Andrew E. Hogan, Jean-Daniel Lelievre, Virginie Gautier, Oliver A. Cornely, Patrick W. G. Mallon, The All Ireland Infectious Diseases Cohort Study, and VACCELERATE Consortium EU-COVAT-1-AGED Part A Study Group

Subjects
Science
Abstract

Abstract SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50

Published
2023
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42. Risk factors for intra-abdominal fungal infection after simultaneous pancreas-kidney transplantation: A single-center retrospective experience

Author

Giovanna Melica, Françoise Botterel, Marie Matignon, C. Angebault, Nawel Aït-Ammar, S. Gallien, Jean-Daniel Lelièvre, Laurent Salomon, Philippe Grimbert, Raphaël Lepeule, and Clara Flateau

Subjects
medicine.medical_specialty, Necrosis, Direct examination, Peritonitis, 030230 surgery, Single Center, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Candida albicans, Pancreas, Retrospective Studies, Transplantation, biology, business.industry, medicine.disease, biology.organism_classification, Thrombosis, Geotrichum, Kidney Transplantation, Infectious Diseases, Mycoses, 030211 gastroenterology & hepatology, medicine.symptom, Complication, business
Abstract

Background Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce. Materials/methods A retrospective monocentric study was conducted on all patients who underwent simultaneous PKT from January 2007 to December 2016. Deep sites positive cultures for fungi during the first post-transplantation year were collected. Clinical, radiological, and microbiological data of proven and probable invasive fungal infections were analysed. Results Among sixteen PKT patients, 15 were included. Seven patients (47%) developed an invasive fungal infection, exclusively IAFI (six proven, one probable). The proven IAFI included four peritonitis, one pancreatic necrosis with infected hematoma, and one patient with positive preservation fluid only (PF). Candida albicans (n = 4) was the most prevalent species (associated with Galactomyces candidus in one case), C glabrata, C dubliniensis, and C krusei were found in one case each. Three patients had either a positive direct examination and/or culture for renal or pancreatic PF and the culture of PF was positive for the same species that caused IAFI. IAFIs were significantly associated with pancreatic graft arterial thrombosis (5/7 vs 0/8, P = .007) and fungal contamination of PF (3/7 vs 0/8, P = .008). Among patients with IAFI, all required an early surgical revision post-transplantation [1-18 days] and six had early or delayed pancreatic graft removal. One patient died in the first post-transplant year. Conclusion IAFI is a common complication in PKT, associated with pancreatic graft thrombosis or fungal contamination of the graft PF, and can sometimes lead to pancreatic detransplantation.

Published
2020

43. Hair follicle stem cell replication stress drives IFI16/STING-dependent inflammation in hidradenitis suppurativa

Author

Yves Levy, Yamina Bennasser, Michele Boniotto, Monsef Benkirane, Pierre Wolkenstein, Cindy Orvain, Hakim Hocini, Jean-Daniel Lelièvre, Sophie Hue, Yea-Lih Lin, Barbara Hersant, Cécile Lefebvre, Claire Hotz, Pascaline Tisserand, Philippe Pasero, Nicolas Ortonne, Francette Jean-Louis, Vaccine Research Institute (VRI), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
0301 basic medicine, Adult, DNA Replication, Male, Adolescent, [SDV]Life Sciences [q-bio], Inflammation, Ataxia Telangiectasia Mutated Proteins, Biology, Outer root sheath, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hidradenitis suppurativa, Progenitor cell, ComputingMilieux_MISCELLANEOUS, integumentary system, Stem Cells, Membrane Proteins, Nuclear Proteins, General Medicine, Cell cycle, Middle Aged, medicine.disease, Hair follicle, Phosphoproteins, Hidradenitis Suppurativa, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Checkpoint Kinase 1, Cancer research, Female, medicine.symptom, Stem cell, Hair Follicle, Adult stem cell, Research Article, DNA Damage
Abstract

Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease. HS appears to be a primary abnormality in the pilosebaceous-apocrine unit. In this work, we characterized hair follicle stem cells (HFSCs) isolated from HS patients and more precisely the outer root sheath cells (ORSCs). We showed that hair follicle cells from HS patients had an increased number of proliferating progenitor cells and lost quiescent stem cells. Remarkably, we also showed that the progression of replication forks was altered in ORSCs from hair follicles of HS patients, leading to activation of the ATR/CHK1 pathway. These alterations were associated with an increased number of micronuclei and with the presence of cytoplasmic ssDNA, leading to the activation of the IFI16/STING pathway and the production of type I IFNs. This mechanistic analysis of the etiology of HS in the HFSC compartment establishes a formal link between genetic predisposition and skin inflammation observed in HS.

Published
2020

44. [Vaccine of the future]

Author

Jean-Daniel, Lelièvre

Subjects
DNA vaccine, vecteurs viraux, pathogènes émergents, reverse vaccinology, viral vectors, RNA vaccine, vaccinologie inverse, vaccin ARN, Article, vaccin ADN, emerging infectious diseases
Abstract

Résumé La vaccination représente une des avancées majeures dans le domaine de la santé. Les premiers vaccins ont été produits sur un concept assez empirique reposant sur la stratégie des « 3 i » : isolement, inactivation, injection. Plus récemment sont apparus les vaccins protéiques. Cependant l’émergence de nouveaux pathogènes, l’inefficacité des stratégies vaccinales actuelles pour protéger contre certaines infections, la nécessité de pouvoir développer rapidement et à bas coût de revient des vaccins ont conduit à développer de nouveaux types de vaccins. C’est dans ce contexte que se sont développés des vaccins basés sur l’utilisation des séquences codantes d’acides nucléiques des antigènes d’intérêt (vecteurs viraux, vaccins ADN, vaccins ARN) visant à améliorer l’efficacité des vaccins actuellement disponibles et à proposer des plateformes génériques potentiellement utilisables contre un grand nombre de pathogènes différents. Outre l’utilisation de ces nouveaux vaccins, les recherches vaccinales en cours bénéficient d’évolutions technologiques visant à délivrer de manière optimale les vaccins, en ciblant par exemple les cellules dendritiques, et de mieux caractériser les antigènes d’intérêt via notamment l’utilisation de la vaccinologie inverse.

Published
2020

45. Characterization of Physicians That Might Be Reluctant to Propose HIV Cure-Related Clinical Trials with Treatment Interruption to Their Patients? The ANRS-APSEC Study

Author

Marie Suzan-Monti, Laurence Meyer, Lisa Fressard, Christel Protière, Marion Mora, Bruno Spire, Marie Préau, Jean-Daniel Lelièvre, Olivier Lambotte, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), The Apsec Study Group, and Dupuis, Christine

Subjects
0301 basic medicine, medicine.medical_specialty, physicians, principal component analysis, [SDV]Life Sciences [q-bio], Immunology, Human immunodeficiency virus (HIV), HIV cure-related clinical trials, lcsh:Medicine, Scientific literature, medicine.disease_cause, Article, analytical treatment interruption studies, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, medicine, Antiretroviral treatment, Pharmacology (medical), 030212 general & internal medicine, Hiv transmission, Pharmacology, business.industry, lcsh:R, Viewpoints, Continuous training, 3. Good health, HIV cure research, [SDV] Life Sciences [q-bio], Clinical trial, 030104 developmental biology, Infectious Diseases, Treatment interruption, Family medicine, multivariable linear regression, business, viewpoints
Abstract

International audience; HIV cure-related clinical trials (HCRCT) with analytical antiretroviral treatment interruptions (ATIs) have become unavoidable. However, the limited benefits for participants and the risk of HIV transmission during ATI might negatively impact physicians' motivations to propose HCRCT to patients. Between October 2016 and March 2017, 164 French HIV physicians were asked about their level of agreement with four viewpoints regarding HCRCT. A reluctance score was derived from their answers and factors associated with reluctance identified. Results showed the highest reluctance to propose HCRCT was among physicians with a less research-orientated professional activity, those not informing themselves about cure trials through scientific literature, and those who participated in trials because their department head asked them. Physicians' perceptions of the impact of HIV on their patients' lives were also associated with their motivation to propose HCRCT: those who considered that living with HIV means living with a secret were more motivated, while those worrying about the negative impact on person living with HIV's professional lives were more reluctant. Our study highlighted the need to design a HCRCT that minimizes constraints for participants and for continuous training programs to help physicians keep up-to-date with recent advances in HIV cure research.

Published
2020

46. Who are the persons living with HIV who might refuse to participate in HIV cure-related clinical trials with treatment interruption?

Author

Marie Préau, Jean-Daniel Lelièvre, Olivier Lambotte, Abdourahmane Sow, Bruno Spire, Lisa Fressard, Marion Mora, Marie Suzan-Monti, Christel Protière, Marion Fiorentino, and Laurence Meyer

Subjects
0301 basic medicine, medicine.medical_specialty, Biomedical Research, Anti-HIV Agents, Immunology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Medicine, Humans, In patient, 030212 general & internal medicine, Intensive care medicine, Clinical Trials as Topic, business.industry, Therapeutic Human Experimentation, 3. Good health, Clinical trial, 030104 developmental biology, Infectious Diseases, Treatment interruption, Patient Participation, business
Abstract

Achieving a HIV cure has become a research priority. As any improvement of knowledge, which could help scientists design new HIV cure-related clinical trials (HCRCT) depends on the risks potential participants are willing to accept, it is important to understand who will agree or refuse to participate and in which proportions. By providing insights into factors associated with reluctance toward HCRCT participation, our results may help clinicians in patient recruitment.

Published
2020

47. Cannabis Use and Plasma Human Immunodeficiency Virus (HIV) RNA Levels in Patients Coinfected With HIV and Hepatitis C Virus Receiving Antiretroviral Therapy: Data From the ANRS CO13 HEPAVIH Cohort

Author

M Chalouni, D Vittecocq, C Rouzaud, C Gilbert, P Bellecave, H Stitou, Thoirain-Galvan, F Touam, C Debreux, D Croisier-Bertin, S Gillet, A de Monte, Patrick Miailhes, F Valour, M L Batard, Lionel Piroth, Joseph Koffi, Y Baazia, Dominique Salmon-Ceron, Morane Cavellec, Gilles Peytavin, B Spire, H Dutronc, C Partouche, Lawrence Serfaty, M Brollo, G Melica, P Catalan, Pascale Trimoulet, P Fischer, David Boutoille, A Mélard, M Mora, P Callard, C Tumiotto, Marianne Maynard, P Bertheau, L Lacaze-Buzy, M Nishimwe, T Pistone, S Fourati, F Roustant, Fabienne Marcellin, Chambrin, S Galim, J Haudebourg, L Traore, S Dominguez, Claudine Duvivier, Brodard, C Rivoisy, M Pauchard, H Laroche, C Katlama, C Allavena, Jean-Daniel Lelièvre, S Fafi-Kremer, K. Barange, S Anriamiandrisoa, D Lacoste, M Desvallees, Karine Lacombe, Marianne Ziol, P Duffau, M Baudoin, Laurent Alric, Y Lévy, Laurent Cotte, Athenaïs Gerber, Rio, P Fisher, C Deback, P Thilbaut, C Louisin, P Platterier, F. Boufassa, Jacques Izopet, S Tezkratt, Reliquet, Philippe Lack, Yazdan Yazdanpanah, Olivier Lortholary, C Pallier, Isabelle Poizot-Martin, S Caldato, Pierre-Marie Girard, A Joulie, P Tremeaux, F Bendjaballah, Julie Chas, François Bailly, J Krause, J Polo Devoto, N Hall, J F Paccalin, Eric Billaud, Yves Benhamou, E Bedel, D. Neau, Tangui Barré, S Gohier, A. Bicart-See, David Zucman, S. Radenne, A S Lascaux, S Ogoudjobi, M L Chaix, C Majerholc, D Malvy, B Marchou, S Reigadas, F Biron, Brigitte Autran, Amaury Martin, C Greib, J Lourenco, Félix Bonnet, E Blanchard, S Bouchez, J Selves, F Dauchy, C Viala, Tristan Ferry, M Partisani, F Marcellin, D. Zucman, D Lambert, Y Ousidhoum, F Z Makhoukhi, P Roux, I Faure, Firouzé Bani-Sadr, Vincent Di Beo, C Le Pendeven, C Protopopescu, M Hentzien, M Le Cam, C Pignon, M Mebarki, A-S Ritleg, M Vandenhende, Hélène Fontaine, Philippe Morlat, C Martins, Marc-Antoine Valantin, Iwaka-Bande, André Boibieux, S Castet-Lafarie, A. Naqvi, Patrice Cacoub, L. Wittkop, A Rodallec, H. Aumaitre, Melina Erica Santos, Dominique Wendum, Petrov-Sanchez, Linda Wittkop, L Berroukeche, I Kansau, D Beniken, Constance Delaugerre, E Farfour, Philippe Sogni, M Buisson, Majid Amiri, François Raffi, David Rey, A Salmon Rousseau, Patrick Mercié, L Le Guen, C Cazanave, Pascal Chavanet, M Santos, Conte, S Akel, P Mercié, E de Mautort, L Chalal, Avettand-Fenoel, Caroline Scholtes, J Zelie, S Nafissa, J F Viallard, D. Lebrasseur-Longuet, Di Beo, Y Nguyen, A Soria, J Adam, C Biron, B Terris, Sarah Maylin, M Favier, Jean-Michel Molina, T Lemboub, Giordanengo, I Kmiec, C. Solas, L Michel, F Charlotte, A.M. Roque, M Hessamfar, C Augustin-Normand, Cécile Goujard, J L Berger, S Breau, H Hue, Sicart-Payssan, J L Pellegrin, P Cervera, A Desclaux, R Bayoud, A. Simon, M Uzan, M Priester, C Cheneau, Caroline Lascoux-Combe, C Chesnel, S Abgrall, M Duong Van Huyen, N Bernard, D Garipuy, E Gardiennet, D Peyramond, D Bornarel, Michel Dupon, F Larroquette, O Zaegel, P Gantner, C Lions, A Waldner-Combernoux, P Miailhes, A Ivanova, Christian Chidiac, Fabien Zoulim, M Mole, R Ben Rayana, H Adle-Biassette, François Nicot, L Esterle, L Meyer, Martinez, F Ader, A Adda-Lievin, P Carrieri, A. Gervais, C Martell, S Mahy, E Lazzaro, P Sogni, T Barré, R Knight, M C Pertusa, J. Bottero, Patrizia Carrieri, T Perpoint, Olivier Bouchaud, D Costagliola, C Gatey, E. Rosenthal, Dominique Salmon, S Lepuil, L Dequae-Merchadou, E Teicher, S Parlier, C Bolliot, G Alexandre, Sophie Metivier, O Braik, M C Receveur, Corinne Brochier, C Hemon, R Usubillaga, François Boué, M Méchain, Camelia Protopopescu, A Ochoa, Catherine Tamalet, M J Ferro-Collados, M P Pietri, P Bioulac-Sage, M C Saint-Paul, T T Le-Thi, M Lefebvre, Paradis, Le Baut, Chloe Pomes, Y Quertainmont, C Bernard-Henry, C Amiel, Gilles Pialoux, R Fior, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Service des maladies infectieuses et tropicales [CH Lyon Sud - HCL] (Hôpital de la Croix-Rousse), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dupuis, Christine, INSERM U1197, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]

Subjects
Microbiology (medical), Hepatitis C virus, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), 030508 substance abuse, HIV Infections, Hepacivirus, medicine.disease_cause, 03 medical and health sciences, Plasma, 0302 clinical medicine, medicine, Humans, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Cannabis, business.industry, Coinfection, HIV, Cannabis use, Hepatitis C, Chronic, Virology, Antiretroviral therapy, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Cohort, RNA, 0305 other medical science, business
Abstract

International audience; No abstract available

Published
2020

48. Analyzing cellular immunogenicity in vaccine clinical trials: a new statistical method including non-specific responses for accurate estimation of vaccine effect

Author

Jean-Daniel Lelièvre, Rodolphe Thiébaut, Aurélie Wiedemann, Edouard Lhomme, Christine Lacabaratz, Laura Richert, Boris P. Hejblum, Yves Levy, CHU de Bordeaux Pellegrin [Bordeaux], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université de Bordeaux (UB), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hejblum, Boris

Subjects
0301 basic medicine, Adult, Male, Computer science, T-Lymphocytes, Immunology, Datasets as Topic, HIV Infections, Computational biology, Bivariate analysis, Models, Biological, Statistical power, 03 medical and health sciences, 0302 clinical medicine, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Immunogenicity, Vaccine, Antigen, Linear regression, Immunology and Allergy, Humans, Computer Simulation, HIV vaccine, Randomized Controlled Trials as Topic, AIDS Vaccines, Immunity, Cellular, [STAT.ME] Statistics [stat]/Methodology [stat.ME], Immunogenicity, Subtraction, Flow Cytometry, Healthy Volunteers, 3. Good health, SISTM, Clinical trial, Benchmarking, 030104 developmental biology, Treatment Outcome, Research Design, HIV-1, Linear Models, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, [STAT.ME]Statistics [stat]/Methodology [stat.ME], 030215 immunology
Abstract

International audience; Evaluation of immunogenicity is a key step in the clinical development of novel vaccines. T-cell responses to vaccine candidates are typically assessed by intracellular cytokine staining (ICS) using multiparametric flow cytometry. A conventional statistical approach to analyze ICS data is to compare, between vaccine regimens or between baseline and post-vaccination of the same regimen depending on the trial design, the percentages of cells producing a cytokine of interest after ex vivo stimulation of peripheral blood mononuclear cells (PBMC) with vaccineantigens, after subtracting the non-specific response (of unstimulated cells) of each sample. Subtraction of the non-specific response is aimed at capturing the specific response to the antigen, but raises methodological issues related to measurement error and statistical power. We describe here a new statistical approach to analyze ICS data from vaccine trials. We propose a bivariate linear random-effect regression model for estimating the nonspecificand antigen-specific ICS responses. We benchmarked the performance of the model in terms of both bias and control of type-I and -II errors in comparison with conventional approaches, and applied it to simulated data as well as real pre- and post-vaccination data from two recent HIV vaccine trials (ANRS VRI01 in healthy volunteers and therapeutic VRI02 ANRS 149 LIGHT in HIV-infected participants). The model was as good as the conventional approaches (with or without subtraction of the non-specific response) in all simulation scenarios in terms of statistical performance, whereas the conventional approaches did not provide robust results across all scenarios. The proposed model estimated the T-cell responses to the antigens without any effect of the nonspecific response on the specific response, irrespective of the correlation between the nonspecific and specific responses. This novel method of analyzing T-cell immunogenicity data based on bivariate modelling allows consideration of all T-cell data and is more flexible than conventional methods, and so yields more detailed results and enables accurate interpretation of vaccine efficacy.

Published
2020

49. Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial

Author

Jean-Daniel Lelièvre, Ralf Wagner, Hans Wolf, Pierre-Alexandre Bart, Bernd Salzberger, Nicole L. Yates, Georgia D. Tomaras, Yves Levy, Aurélie Wiedemann, Rodolphe Thiébaut, Raphael Gottardo, Wolfgang Stöhr, David M. Koelle, Sheena McCormack, Véronique Rieux, Song Ding, Giuseppe Pantaleo, Christine Lacabaratz, Kim Ellefsen-Lavoie, Odile Launay, Bryan T. Mayer, David C. Montefiori, Geneviève Chêne, Mathieu Surenaud, Jonathan Weber, DARMIGNY, SANDRINE, Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University College of London [London] (UCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imperial College London, University of Washington [Seattle], Universität Regensburg (UR), Duke University Medical Center, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), EuroVacc Foundation (EVF), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Henri Mondor [Créteil]

Subjects
RNA viruses, Male, Physiology, HIV Antigens, [SDV]Life Sciences [q-bio], Antibody Response, Priming (immunology), CD8-Positive T-Lymphocytes, Pathology and Laboratory Medicine, Biochemistry, White Blood Cells, Immunodeficiency Viruses, Animal Cells, 1108 Medical Microbiology, Immune Physiology, Medicine and Health Sciences, Vaccines, DNA, Clinical endpoint, Cytotoxic T cell, Enzyme-Linked Immunoassays, HIV vaccine, Biology (General), Immune Response, ComputingMilieux_MISCELLANEOUS, AIDS Vaccines, Vaccines, Innate Immune System, 0303 health sciences, Immune System Proteins, biology, T Cells, ELISPOT, 030302 biochemistry & molecular biology, env Gene Products, Human Immunodeficiency Virus, T-Lymphocytes, Helper-Inducer, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.anatomical_structure, Medical Microbiology, 1107 Immunology, Viral Pathogens, Viruses, Cytokines, Female, Cellular Types, Pathogens, Antibody, Research Article, 0605 Microbiology, Adult, Infectious Disease Control, Adolescent, QH301-705.5, Immune Cells, T cell, Genetic Vectors, Immunology, Research and Analysis Methods, Microbiology, Antibodies, Interferon-gamma, 03 medical and health sciences, Virology, Retroviruses, Genetics, medicine, Humans, Immunoassays, Microbial Pathogens, Molecular Biology, 030304 developmental biology, Blood Cells, business.industry, Poxviridae, Lentivirus, Organisms, Biology and Life Sciences, Proteins, HIV, Cell Biology, Molecular Development, RC581-607, Regimen, Immune System, Immunologic Techniques, biology.protein, Parasitology, Immunologic diseases. Allergy, business, Developmental Biology
Abstract

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P, Author summary Development of a safe and effective HIV-1 vaccine would undoubtedly be the best solution for the ultimate control of the worldwide AIDS pandemic. To date, only one large phase III trial (RV144 Thai study) showed a partial and modest protection against HIV infection. This result raised hope in the field and encouraged the development of vaccines or strategies in order to improve vaccine efficacy. Several vaccine strategies designed to elicit broad HIV-specific T cells and/or neutralizing antibodies to prevent HIV-1 transmission are under evaluation. Among diverse candidate vaccines, the safety and immunogenicity of multi-gene DNA-based and Pox-virus derived vaccines have been evaluated in several clinical studies. The present study was designed to optimize the combination of these two vaccines with the aim of determining the optimal number of DNA primes for a poxvirus-based HIV vaccine regimen. We show here that the prime boost combination is highly immunogenic and that the number of DNA primes induces differentially T cell and antibody responses. A better priming of poxvirus-based vaccine regimens for T cells is obtained with 3 DNA injections. Our results contribute and extend data of several preclinical studies pointing out the potential interest of DNA as a prime capable not only of improving immune responses but also of imprinting the long-term responses to boost vaccines.

Published
2020

50. Hospitalization of HIV positive patients: Significant demand affecting all hospital sectors

Author

François Boué, Claudine Duvivier, Laurence Weiss, A Sobel, C Rapp, D Vittecoq, Rémonie Seng, Dominique Salmon, Julien Riou, G Brucker, Cécile Goujard, J Frenkiel, Laurence Meyer, M Frank-Soltysiak, Jean-Daniel Lelièvre, O Zak Dit Zbar, P Mutuon, and Corevih

Subjects
Adult, Male, 0301 basic medicine, Paris, medicine.medical_specialty, Referral, Epidemiology, Hospital Departments, HIV Infections, Context (language use), Comorbidity, Young Adult, 03 medical and health sciences, medicine, Humans, Young adult, Health Services Needs and Demand, AIDS-Related Opportunistic Infections, business.industry, Medical record, Public Health, Environmental and Occupational Health, Length of Stay, Middle Aged, medicine.disease, 030112 virology, Hospitalization, Emergency medicine, Ambulatory, HIV-1, Coinfection, Female, business, Delivery of Health Care, Dyslipidemia
Abstract

Background In a context of the evolution of severe morbidities in patients living with HIV (PLWH), the aim of this study was to describe reasons for hospitalization and the mode of care for the patients requiring hospitalization. Methods All admissions (≥ 24 h) of PLWH to 10 hospitals in the south of Paris (COREVIH Ile-de-France Sud) between 1/1/2011 and 12/31/2011 were identified. The hospital database and the file of patients followed in the HIV referral department of each hospital were matched. Detailed clinical and biological data were collected, by returning to the individual medical records, for a random sample (65% of hospitalized patients). Results A total of 3013 hospitalizations (1489 patients) were recorded in 2011. The estimated rate of hospitalized patients was about 8% among the 10105 PLWH routinely managed in COREVIH Ile-de-France Sud in 2011. The majority (58.5%) of these hospitalizations occurred in a unit other than the HIV referral unit. Non-AIDS-defining infections were the main reason for admission (16.4%), followed by HIV-related diseases (15.6%), hepatic/gastrointestinal diseases (12.0%), and cardiovascular diseases (10.3%). The median length of stay was 5 days overall (IQR: 2-11), it was longer among patients admitted to a referral HIV care unit than to another ward. HIV infection had been diagnosed > 10 years previously in 61.4% of these hospitalized patients. They often had associated comorbidities (coinfection HCV/HVB 40.5%, smoking 45.8%; hypertension 33.4%, dyslipidemia 28.8%, diabetes 14.8%). Subjects over 60 years old accounted for 15% of hospitalized patients, most of them were virologically controlled under HIV treatment, and cardiovascular diseases were their leading reason for admission. Conclusion Needs for hospitalization among PLWH remain important, with a wide variety in causes of admission, involving all hospital departments. It is essential to prevent comorbidities to reduce these hospitalizations, and to maintain a link between the management of PLWH, that becomes rightly, increasing ambulatory, and recourse to specialized inpatient services.

Published
2018

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