Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study
Year: 2019
Type: article
Study design: Observational Study
Abstract: BACKGROUND: In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children <18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciz253
Authors: Elizabeth Chappell, Andrew Riordan, Gonzague Jourdain, Antoni Soriano-Arandes, Luminita Ene, Henriette J Scherpbier, Josiane Warszawski, Intira J Collins, Colette Smit, Laura Marques, Nigel Klein, Sara Guillén, Ali Judd, Claire Thorne, Ruth Goodall, Christoph Königs, Vana Spoulou, Filipa Prata, Tessa Goetghebuer, Elena Chiappini, Luisa Galli, Lars Naver, Carlo Giaquinto, Diana M Gibb, Magdalena Marczynska, Liubov Okhonskaia, Thomas Klimkait, Marc Lallemant, Nicole Ngo-Giang-Huong, Galyna Kiseleva, Ruslan Malyuta, Alla Volokha, Tessa Goetghebuer, Marc Hainaut, Marc Delforge, Josiane Warszawski, Jerome Le Chenadec, Elisa Ramos, Olivia Dialla, Thierry Wack, Corine Laurent, Lamya Ait si Selmi, Isabelle Leymarie, Fazia Ait Benali, Maud Brossard, Leila Boufassa, Corinne Floch-Tudal, Ghislaine Firtion, Isabelle Hau, Anne Chace, Pascal Bolot, Stéphane Blanche, Martine Levine, Le Kremlin Bicëtre, Corinne Fourcade, Brigitte Heller-Roussin, Camille Runel-Belliard, Joëlle Tricoire, Catherine Chirouze, Véronique Reliquet, Jacques Brouard, Kamila Kebaili, Pascale Fialaire, Muriel Lalande, Christoph Königs, Stephan Schultze-Strasser, U Baumann, T Niehues, J Neubert, R Kobbe, Charite Berlin, C Feiterna-Sperling, C Königs, B Buchholz, G Notheis, Vana Spoulou, Maurizio de Martino, Pier Angelo Tovo, Osimani Patrizia, Domenico Larovere, Maurizio Ruggeri, Giacomo Faldella, Francesco Baldi, Raffaele Badolato, Carlotta Montagnani, Elisabetta Venturini, Catiuscia Lisi, Antonio Di Biagio, Lucia Taramasso, Vania Giacomet, Paola Erba, Susanna Esposito, Rita Lipreri, Filippo Salvini, Claudia Tagliabue, Monica Cellini, Eugenia Bruzzese, Andrea Lo Vecchio, Osvalda Rampon, Daniele Donà, Amelia Romano, Icilio Dodi, Anna Maccabruni, Rita Consolini, Stefania Bernardi, Hyppolite Tchidjou Kuekou, Orazio Genovese, Paolina Olmeo, Letizia Cristiano, Antonio Mazza, Clara Gabiano, Silvia Garazzino, Antonio Pellegatta, D Pajkrt, H J Scherpbier, A M Weijsenfeld, C G de Boer, S Jurriaans, N K T Back, H L Zaaijer, B Berkhout, M T E Cornelissen, C J Schinkel, K C Wolthers, P L A Fraaij, A M C van Rossum, L C van der Knaap, E G Visser, M P G Koopmans, J J A van Kampen, S D Pas, S S V Henriet, M van de Flier, K van Aerde, R Strik-Albers, J Rahamat-Langendoen, F F Stelma, E H Schölvinck, H de Groot-de Jonge, H G M Niesters, C C van Leer-Buter, M Knoester, L J Bont, S P M Geelen, T F W Wolfs, N Nauta, C W Ang, R van Houdt, A M Pettersson, C M J E Vandenbroucke-Grauls, P Reiss, D O Bezemer, A I van Sighem, C Smit, F W M N Wit, T S Boender, S Zaheri, M Hillebregt, A de Jong, D Bergsma, S Grivell, A Jansen, M Raethke, R Meijering, L de Groot, M van den Akker, Y Bakker, E Claessen, A El Berkaoui, J Koops, E Kruijne, C Lodewijk, L Munjishvili, B Peeck, C Ree, R Regtop, Y Ruijs, T Rutkens, M Schoorl, A Timmerman, E Tuijn, L Veenenberg, S van der Vliet, A Wisse, T Woudstra, B Tuk, Jolanta Popielska, Maria Pokorska-Śpiewak, Agnieszka Ołdakowska, Konrad Zawadka, Urszula Coupland, Małgorzata DorobaLaura Marques, Carla Teixeira, Alexandre Fernandes, Filipa Prata, Luminita Ene, Liubov Okhonskaia, Evgeny Voronin, Milana Miloenko, Svetlana Labutina, José Tomás Ramos, Luis Prieto, Sara Guillén, María Luisa Navarro, Jesús Saavedra, Mar Santos, Mª Angeles Muñoz, Beatriz Ruiz, Carolina Fernandez Mc Phee, Santiago Jimenez de Ory, Susana Alvarez, Miguel Ángel Roa, José Beceiro, Jorge Martínez, Katie Badillo, Miren Apilanez, Itziar Pocheville, Elisa Garrote, Elena Colino, Jorge Gómez Sirvent, Mónica Garzón, Vicente Román, Abián Montesdeoca, Mercedes Mateo, María José Muñoz, Raquel Angulo, Olaf Neth, Lola Falcón, Pedro Terol, Juan Luis Santos, David Moreno, Francisco Lendínez, Ana Grande, Francisco José Romero, Miguel Lillo, Begoña Losada, Mercedes Herranz, Matilde Bustillo, Carmelo Guerrero, Pilar Collado, José Antonio Couceiro, Amparo Pérez, Ana Isabel Piqueras, Rafael Bretón, Inmaculada Segarra, César Gavilán, Enrique Jareño, Elena Montesinos, Marta Dapena, Cristina Álvarez, Ana Gloria Andrés, Víctor Marugán, Carlos Ochoa, Santiago Alfayate, Ana Isabel Menasalvas, Elisa de Miguel, K Aebi-Popp, S Asner, V Aubert, M Battegay, M Baumann, E Bernasconi, J Böni, P Brazzola, H C Bucher, A Calmy, M Cavassini, A Ciuffi, A Duppenthaler, G Dollenmaier, M Egger, L Elzi, J Fehr, J Fellay, K Francini, H Furrer, C A Fux, C Grawe, H F Günthard, D Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, C Kahlert, L Kaiser, O Keiser, T Klimkait, H Kovari, R D Kouyos, B Ledergerber, G Martinetti, B Martinez de Tejada, K J Metzner, N Müller, D Nicca, P Paioni, G Pantaleo, Ch Polli, K Posfay-Barbe, A Rauch, C Rudin, P Schmid, A U Scherrer, R Speck, P Tarr, M Thanh Lecompte, A Trkola, P Vernazza, N Wagner, G Wandeler, R Weber, C A Wyler, S Yerly, Pornchai Techakunakorn, Rawiwan Hansudewechakul, Chiang Kham, Vanichaya Wanchaitanawong, Sookchai Theansavettrakul, Mae Sai, Sirisak Nanta, Chaiwat Ngampiyaskul, Siriluk Phanomcheong, Suchat Hongsiriwon, Warit Karnchanamayul, Ratchanee Kwanchaipanich, Suparat Kanjanavanit, Nareerat Kamonpakorn, Maneeratn Nantarukchaikul, Prapaisri Layangool, Jutarat Mekmullica, Paiboon Lucksanapisitkul, Sudarat Watanayothin, Narong Lertpienthum, Boonyarat Warachit, Sansanee Hanpinitsak, Sathit Potchalongsin, Pimpraphai Thanasiri, Sawitree Krikajornkitti, Pornsawan Attavinijtrakarn, Sakulrat Srirojana, Suthunya Bunjongpak, Achara Puangsombat, Sathaporn Na-Rajsima, Pornchai Ananpatharachai, Noppadon Akarathum, Vachira Phuket, Weerasak Lawtongkum, Prapawan Kheunjan, Thitiporn Suriyaboon, Airada Saipanya, Kanchana Than-in-at, Nirattiya Jaisieng, Rapeepan Suaysod, Sanuphong Chailoet, Naritsara Naratee, Suttipong Kawilapat, T Kaleeva, Y Baryshnikova, S Soloha, N Bashkatova, I Raus, O Glutshenko, Z Ruban, N Prymak, G Kiseleva, H Bailey, Alasdair Bamford, Karina Butler, Katja Doerholt, Conor Doherty, Caroline Foster, Kate Francis, Ian Harrison, Julia Kenny, Nigel Klein, Gillian Letting, Paddy McMaster, Fungai Murau, Edith Nsangi, Helen Peters, Katia Prime, Andrew Riordan, Fiona Shackley, Delane Shingadia, Sharon Storey, Claire Thorne, Gareth Tudor-Williams, Anna Turkova, Steve Welch, Intira Jeannie Collins, Claire Cook, Siobhan Crichton, Donna Dobson, Keith Fairbrother, Diana M Gibb, Lynda Harper, Ali Judd, Marthe Le Prevost, Nadine Van Looy, Helen Peters, Claire Thorne, K Butler, A Walsh, L Thrasyvoulou, S Welch, J Bernatoniene, F Manyika, G Sharpe, B Subramaniam, K Sloper, K Fidler, R Hague, V Price, M Clapson, J Flynn, A Cardoso, M Abou-Rayyah, N Klein, D Shingadia, D Gurtin, S Yeadon, S Segal, C Ball, S Hawkins, M Dowie, S Bandi, E Percival, M Eisenhut, K Duncan, S Clough, L Anguvaa, S Conway, T Flood, A Pickering, P McMaster, C Murphy, J Daniels, Y Lees, F Thompson, B Williams, S Pope, L Cliffe, A Smyth, S Southall, A Freeman, H Freeman, S Christie, A Gordon, D Rogahn, L Clarke, L Jones, B Offerman, M Greenberg, C Benson, A Riordan, L Ibberson, F Shackley, S N Faust, J Hancock, K Doerholt, K Prime, M Sharland, S Storey, H Lyall, C Monrose, P Seery, G Tudor-Williams, E Menson, A Callaghan, A Bridgwood, P McMaster, J Evans, E Blake, A Yannoulias, Elizabeth Chappell, Siobhan Critchton, Intira Jeannie Collins, Charlotte Duff, Carlo Giaquinto, Ruth Goodall, Daniel Gomezpena, Ali Judd, Rebecca Lundin, Laura Mangiarini, Alessandra Nardone, Claire Thorne
Institutions: MRC Clinical Trials Unit at UCL, University College London, Centre de recherche en Epidémiologie et Santé des Populations, Stichting HIV Monitoring, Universidad de Alcalá, Université Grenoble Alpes, University Hospital Frankfurt, University of Florence, University of Padua, University of Basel, Institut de Recherche pour le Développement, Centre Hospitalier Saint-Denis, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, Centre Hospitalier Universitaire de Besançon, Laboratoire Chrono-Environnement, Centre Hospitalier Universitaire de Nantes, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Universitaire de Montpellier, University of Milan, University of Parma, University of Twente, Institut de Génétique Humaine, Architecture et Réactivité de l'arN, Institut de Biologie Moléculaire et Cellulaire, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Universidade Federal do Ceará, Universidade de Vigo, Universitat Politècnica de València, University of the Basque Country, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Prapokklao Hospital, Nakornping Hospital, Samut Sakhon Hospital, Kalasin Hospital, SanPaTong Hospital, Chiang Mai University, University of Edinburgh, European Synchrotron Radiation Facility, UK Centre for Ecology & Hydrology, University of London, London South Bank University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Funders: Styrelsen för Internationellt Utvecklingssamarbete, Gilead Sciences, ViiV Healthcare, Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent, National Institute for Health and Care Research, University College London, European Commission, Institut National de la Santé et de la Recherche Médicale, Ministerie van Volksgezondheid, Welzijn en Sport, Fundación Para La Innovación Y La Prospectiva En Salud En España, Medical Research Council, Instituto de Salud Carlos III, European Regional Development Fund, Janssen Pharmaceuticals
Awards: G1181207585, G1279792896, G1667250455, G1743780862, G2138123561, G2219656881, NIHR Senior Investigator Award, European Network of HIV/AIDS Cohort Studies to Coordinate at European and International Level Clinical Research on HIV/AIDS, G2437151533, G2438162151, G3078245608, G3174094459, Impacto del tratamiento antirretroviral en el SNC del paciente pediátrico con infección VIH. Correlación con neuroimagen y perfil neurocognitivo, G3517080532, G3578120429, G3982095159, G4349345483, G4438663976, G4845781446, Paediatric and adolescent infections, G590453144, G6520461594, G6790473868, G8126766150, G817500610, G8806128818, G8934619222
OpenAlex ID: W2930537672