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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.
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 / Chappell, Elizabeth; Riordan, Andrew; Jourdain, Gonzague; Soriano-Arandes, Antoni; Ene, Luminita; Scherpbier, Henriette J; Warszawski, Josiane; Collins, Intira J; Smit, Colette; Marques, Laura; Klein, Nigel; Guillén, Sara; Judd, Ali; Thorne, Claire; Goodall, Ruth; Königs, Christoph; Spoulou, Vana; Prata, Filipa; Goetghebuer, Tessa; Chiappini, Elena; Galli, Luisa; Naver, Lars; Giaquinto, Carlo; Gibb, Diana M; Marczynska, Magdalena; Okhonskaia, Liubov; Klimkait, Thomas; Lallemant, Marc; Ngo-Giang-Huong, Nicole; Kiseleva, Galyna; Malyuta, Ruslan; Volokha, Alla; Goetghebuer, Tessa; Hainaut, Marc; Delforge, Marc; Warszawski, Josiane; Le Chenadec, Jerome; Ramos, Elisa; Dialla, Olivia; Wack, Thierry; Laurent, Corine; Ait si Selmi, Lamya; Leymarie, Isabelle; Ait Benali, Fazia; Brossard, Maud; Boufassa, Leila; Floch-Tudal, Corinne; Firtion, Ghislaine; Hau, Isabelle; Chace, Anne; Bolot, Pascal; Blanche, Stéphane; Levine, Martine; Bicëtre, Le Kremlin; Fourcade, Corinne; Heller-Roussin, Brigitte; Runel-Belliard, Camille; Tricoire, Joëlle; Chirouze, Catherine; Reliquet, Véronique; Brouard, Jacques; Kebaili, Kamila; Fialaire, Pascale; Lalande, Muriel; Königs, Christoph; Schultze-Strasser, Stephan; Baumann, U; Niehues, T; Neubert, J; Kobbe, R; Berlin, Charite; Feiterna-Sperling, C; Königs, C; Buchholz, B; Notheis, G; Spoulou, Vana; de Martino, Maurizio; Angelo Tovo, Pier; Patrizia, Osimani; Larovere, Domenico; Ruggeri, Maurizio; Faldella, Giacomo; Baldi, Francesco; Badolato, Raffaele; Montagnani, Carlotta; Venturini, Elisabetta; Lisi, Catiuscia; Di Biagio, Antonio; Taramasso, Lucia; Giacomet, Vania; Erba, Paola; Esposito, Susanna; Lipreri, Rita; Salvini, Filippo; Tagliabue, Claudia; Cellini, Monica; Bruzzese, Eugenia; Lo Vecchio, Andrea; Rampon, Osvalda; Donà, Daniele; Romano, Amelia; Dodi, Icilio; Maccabruni, Anna; Consolini, Rita; Bernardi, Stefania; Tchidjou Kuekou, Hyppolite; Genovese, Orazio; Olmeo, Paolina; Cristiano, Letizia; Mazza, Antonio; Gabiano, Clara; Garazzino, Silvia; Pellegatta, Antonio; Pajkrt, D; Scherpbier, H J; Weijsenfeld, A M; de Boer, C G; Jurriaans, S; Back, N K T; Zaaijer, H L; Berkhout, B; Cornelissen, M T E; Schinkel, C J; Wolthers, K C; Fraaij, P L A; van Rossum, A M C; van der Knaap, L C; Visser, E G; Koopmans, M P G; van Kampen, J J A; Pas, S D; Henriet, S S V; van de Flier, M; van Aerde, K; Strik-Albers, R; Rahamat-Langendoen, J; Stelma, F F; Schölvinck, E H; de Groot-de Jonge, H; Niesters, H G M; van Leer-Buter, C C; Knoester, M; Bont, L J; Geelen, S P M; Wolfs, T F W; Nauta, N; Ang, C W; van Houdt, R; Pettersson, A M; Vandenbroucke-Grauls, C M J E; Reiss, P; Bezemer, D O; van Sighem, A I; Smit, C; Wit, F W M N; Boender, T S; Zaheri, S; Hillebregt, M; de Jong, A; Bergsma, D; Grivell, S; Jansen, A; Raethke, M; Meijering, R; de Groot, L; van den Akker, M; Bakker, Y; Claessen, E; El Berkaoui, A; Koops, J; Kruijne, E; Lodewijk, C; Munjishvili, L; Peeck, B; Ree, C; Regtop, R; Ruijs, Y; Rutkens, T; Schoorl, M; Timmerman, A; Tuijn, E; Veenenberg, L; van der Vliet, S; Wisse, A; Woudstra, T; Tuk, B; Popielska, Jolanta; Pokorska-Śpiewak, Maria; Ołdakowska, Agnieszka; Zawadka, Konrad; Coupland, Urszula; DorobaLaura Marques, Małgorzata; Teixeira, Carla; Fernandes, Alexandre; Prata, Filipa; Ene, Luminita; Okhonskaia, Liubov; Voronin, Evgeny; Miloenko, Milana; Labutina, Svetlana; Tomás Ramos, José; Prieto, Luis; Guillén, Sara; Luisa Navarro, María; Saavedra, Jesús; Santos, Mar; Angeles Muñoz, Mª; Ruiz, Beatriz; Mc Phee, Carolina Fernandez; de Ory, Santiago Jimenez; Alvarez, Susana; Ángel Roa, Miguel; Beceiro, José; Martínez, Jorge; Badillo, Katie; Apilanez, Miren; Pocheville, Itziar; Garrote, Elisa; Colino, Elena; Gómez Sirvent, Jorge; Garzón, Mónica; Román, Vicente; Montesdeoca, Abián; Mateo, Mercedes; José Muñoz, María; Angulo, Raquel; Neth, Olaf; Falcón, Lola; Terol, Pedro; Luis Santos, Juan; Moreno, David; Lendínez, Francisco; Grande, Ana; José Romero, Francisco; Lillo, Miguel; Losada, Begoña; Herranz, Mercedes; Bustillo, Matilde; Guerrero, Carmelo; Collado, Pilar; Antonio Couceiro, José; Pérez, Amparo; Isabel Piqueras, Ana; Bretón, Rafael; Segarra, Inmaculada; Gavilán, César; Jareño, Enrique; Montesinos, Elena; Dapena, Marta; Álvarez, Cristina; Gloria Andrés, Ana; Marugán, Víctor; Ochoa, Carlos; Alfayate, Santiago; Isabel Menasalvas, Ana; de Miguel, Elisa; Aebi-Popp, K; Asner, S; Aubert, V; Battegay, M; Baumann, M; Bernasconi, E; Böni, J; Brazzola, P; Bucher, H C; Calmy, A; Cavassini, M; Ciuffi, A; Duppenthaler, A; Dollenmaier, G; Egger, M; Elzi, L; Fehr, J; Fellay, J; Francini, K; Furrer, H; Fux, C A; Grawe, C; Günthard, H F; Haerry, D; Hasse, B; Hirsch, H H; Hoffmann, M; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kovari, H; Kouyos, R D; Ledergerber, B; Martinetti, G; de Tejada, B Martinez; Metzner, K J; Müller, N; Nicca, D; Paioni, P; Pantaleo, G; Polli, Ch; Posfay-Barbe, K; Rauch, A; Rudin, C; Schmid, P; Scherrer, A U; Speck, R; Tarr, P; Thanh Lecompte, M; Trkola, A; Vernazza, P; Wagner, N; Wandeler, G; Weber, R; Wyler, C A; Yerly, S; Techakunakorn, Pornchai; Hansudewechakul, Rawiwan; Kham, Chiang; Wanchaitanawong, Vanichaya; Theansavettrakul, Sookchai; Sai, Mae; Nanta, Sirisak; Ngampiyaskul, Chaiwat; Phanomcheong, Siriluk; Hongsiriwon, Suchat; Karnchanamayul, Warit; Kwanchaipanich, Ratchanee; Kanjanavanit, Suparat; Kamonpakorn, Nareerat; Nantarukchaikul, Maneeratn; Layangool, Prapaisri; Mekmullica, Jutarat; Lucksanapisitkul, Paiboon; Watanayothin, Sudarat; Lertpienthum, Narong; Warachit, Boonyarat; Hanpinitsak, Sansanee; Potchalongsin, Sathit; Thanasiri, Pimpraphai; Krikajornkitti, Sawitree; Attavinijtrakarn, Pornsawan; Srirojana, Sakulrat; Bunjongpak, Suthunya; Puangsombat, Achara; Na-Rajsima, Sathaporn; Ananpatharachai, Pornchai; Akarathum, Noppadon; Phuket, Vachira; Lawtongkum, Weerasak; Kheunjan, Prapawan; Suriyaboon, Thitiporn; Saipanya, Airada; Than-in-at, Kanchana; Jaisieng, Nirattiya; Suaysod, Rapeepan; Chailoet, Sanuphong; Naratee, Naritsara; Kawilapat, Suttipong; Kaleeva, T; Baryshnikova, Y; Soloha, S; Bashkatova, N; Raus, I; Glutshenko, O; Ruban, Z; Prymak, N; Kiseleva, G; Bailey, H; Bamford, Alasdair; Butler, Karina; Doerholt, Katja; Doherty, Conor; Foster, Caroline; Francis, Kate; Harrison, Ian; Kenny, Julia; Klein, Nigel; Letting, Gillian; McMaster, Paddy; Murau, Fungai; Nsangi, Edith; Peters, Helen; Prime, Katia; Riordan, Andrew; Shackley, Fiona; Shingadia, Delane; Storey, Sharon; Thorne, Claire; Tudor-Williams, Gareth; Turkova, Anna; Welch, Steve; Jeannie Collins, Intira; Cook, Claire; Crichton, Siobhan; Dobson, Donna; Fairbrother, Keith; M Gibb, Diana; Harper, Lynda; Judd, Ali; Le Prevost, Marthe; Van Looy, Nadine; Peters, Helen; Thorne, Claire; Butler, K; Walsh, A; Thrasyvoulou, L; Welch, S; Bernatoniene, J; Manyika, F; Sharpe, G; Subramaniam, B; Sloper, K; Fidler, K; Hague, R; Price, V; Clapson, M; Flynn, J; Cardoso, A; Abou-Rayyah, M; Klein, N; Shingadia, D; Gurtin, D; Yeadon, S; SegalC Ball, S; Hawkins, S; Dowie, M; Bandi, S; Percival, E; Eisenhut, M; Duncan, K; Clough, S; Anguvaa, L; Conway, S; Flood, T; Pickering, A; McMaster, P; Murphy, C; Daniels, J; Lees, Y; Thompson, F; Williams, B; Pope, S; Cliffe, L; Smyth, A; Southall, S; Freeman, A; Freeman, H; Christie, S; Gordon, A; Rogahn, D; Clarke, L; Jones, L; Offerman, B; Greenberg, M; Benson, C; Riordan, A; Ibberson, L; Shackley, F; Faust, S N; Hancock, J; Doerholt, K; Prime, K; Sharland, M; Storey, S; Lyall, H; Monrose, C; Seery, P; Tudor-Williams, G; Menson, E; Callaghan, A; Bridgwood, A; McMaster, P; Evans, J; Blake, E; Yannoulias, A; Chappell, Elizabeth; Critchton, Siobhan; Jeannie Collins, Intira; Duff, Charlotte; Giaquinto, Carlo; Goodall, Ruth; Gomezpena, Daniel; Judd, Ali; Lundin, Rebecca; Mangiarini, Laura; Nardone, Alessandra; Thorne, Claire. - In: CLINICAL INFECTIOUS DISEASES. - ISSN 1537-6591. - ELETTRONICO. - 70:(2020), pp. 404-415. [10.1093/cid/ciz253]
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
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.
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