Michael Schomaker1, Valeriane Leroy2, Tom Wolfs3, Karl-Günter Technau4,5, Lorna Renner6, Ali Judd7, Shobna Sawry8, Madeleine Amorissani-Folquet9, Antoni Noguera-Julian10, Frank Tanser11,12,13, François Eboua14, Maria Luisa Navarro15, Cleophas Chimbetete16, Clarisse Amani-Bosse17, Josiane Warszawski18, Sam Phiri19, Sylvie N'Gbeche20, Vivian Cox21, Fla Koueta22, Janet Giddy23, Haby Sygnaté-Sy24, Dorthe Raben25, Geneviève Chêne26,27,28, Mary-Ann Davies1. 1. Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa. 2. Inserm, U1027, Université Paul Sabatier Toulouse 3 Toulouse, France. 3. Children's Hospital/UMCU, Department of Infectious Diseases, Utrecht, The Netherlands. 4. Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa. 5. Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa. 6. University of Ghana Medical School, Accra, Ghana. 7. MRC Clinical Trials Unit, University College London, London, UK. 8. University of the Witwatersrand, Wits Reproductive Health and HIV Institute, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. 9. Félix Houphouët Boigny University Hospital, Abidjan, Côte d'Ivoire. 10. Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain. 11. Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa. 12. School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa. 13. Centre for the AIDS Programme of Research in South Africa - CAPRISA, University of KwaZulu-Natal, Congella, South Africa. 14. Yopougon University Hospital, Abidjan, Côte d'Ivoire. 15. Hospital Gregorio Marañón, Madrid, Spain. 16. Newlands Clinic, Harare, Zimbabwe. 17. MTCT-Plus Center, Abidjan, Côte d'Ivoire. 18. Centre de recherche en épidémiologie et santé des populations, 1018 Inserm, France. 19. Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi. 20. Centre de Prise en Charge de Recherche et de Formation Enfants, Abidjan, Côte d'Ivoire. 21. Médecins Sans Frontiéres South Africa, Cape Town, South Africa. 22. Charles de Gaulle University Hospital, Ouagadougou, Burkina Faso. 23. Sinikithemba Clinic, McCord Hospital, Durban, South Africa. 24. Albert Royer Hospital, Dakar, Senegal. 25. Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 26. University of Bordeaux Bordeaux, ISPED, Centre INSERM U1219-Bordeaux Population Health, F-33000 Bordeaux, France. 27. INSERM, ISPED, Centre INSERM U1219-Bordeaux Population Health, F-33000 Bordeaux, France. 28. CHU de Bordeaux, Pôle de santé publique, Service d information médicale, F-33000 Bordeaux, France.
Abstract
Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm 3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm 3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm 3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm 3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
Authors: Sara Lodi; Andrew Phillips; Roger Logan; Ashley Olson; Dominique Costagliola; Sophie Abgrall; Ard van Sighem; Peter Reiss; José M Miró; Elena Ferrer; Amy Justice; Neel Gandhi; Heiner C Bucher; Hansjakob Furrer; Santiago Moreno; Susana Monge; Giota Touloumi; Nikos Pantazis; Jonathan Sterne; Jessica G Young; Laurence Meyer; Rémonie Seng; Francois Dabis; Marie-Anne Vandehende; Santiago Pérez-Hoyos; Inma Jarrín; Sophie Jose; Caroline Sabin; Miguel A Hernán Journal: Lancet HIV Date: 2015-07-07 Impact factor: 12.767
Authors: Jens D Lundgren; Abdel G Babiker; Fred Gordin; Sean Emery; Birgit Grund; Shweta Sharma; Anchalee Avihingsanon; David A Cooper; Gerd Fätkenheuer; Josep M Llibre; Jean-Michel Molina; Paula Munderi; Mauro Schechter; Robin Wood; Karin L Klingman; Simon Collins; H Clifford Lane; Andrew N Phillips; James D Neaton Journal: N Engl J Med Date: 2015-07-20 Impact factor: 91.245
Authors: Daniel Westreich; Stephen R Cole; Jessica G Young; Frank Palella; Phyllis C Tien; Lawrence Kingsley; Stephen J Gange; Miguel A Hernán Journal: Stat Med Date: 2012-04-11 Impact factor: 2.373
Authors: Paige L Williams; Mark J Abzug; Denise L Jacobson; Jiajia Wang; Russell B Van Dyke; Rohan Hazra; Kunjal Patel; Linda A Dimeglio; Elizabeth J McFarland; Margarita Silio; William Borkowsky; George R Seage; James M Oleske; Mitchell E Geffner Journal: AIDS Date: 2013-07-31 Impact factor: 4.177
Authors: Avy Violari; Mark F Cotton; Diana M Gibb; Abdel G Babiker; Jan Steyn; Shabir A Madhi; Patrick Jean-Philippe; James A McIntyre Journal: N Engl J Med Date: 2008-11-20 Impact factor: 91.245
Authors: Linda Barlow-Mosha; Victor Musiime; Mary-Ann Davies; Andrew J Prendergast; Philippa Musoke; George Siberry; Martina Penazzato Journal: J Int AIDS Soc Date: 2017-06-27 Impact factor: 5.396
Authors: Florian Vogt; Andrea M Rehman; Katharina Kranzer; Mary Nyathi; Johan Van Griensven; Mark Dixon; Wedu Ndebele; Hilary Gunguwo; Robert Colebunders; Mbongeni Ndlovu; Tsitsi Apollo; Rashida A Ferrand Journal: J Acquir Immune Defic Syndr Date: 2017-04-01 Impact factor: 3.731
Authors: Amy L Slogrove; Michael Schomaker; Mary-Ann Davies; Paige Williams; Suna Balkan; Jihane Ben-Farhat; Nancy Calles; Kulkanya Chokephaibulkit; Charlotte Duff; Tanoh François Eboua; Adeodata Kekitiinwa-Rukyalekere; Nicola Maxwell; Jorge Pinto; George Seage; Chloe A Teasdale; Sebastian Wanless; Josiane Warszawski; Kara Wools-Kaloustian; Marcel Yotebieng; Venessa Timmerman; Intira J Collins; Ruth Goodall; Colette Smith; Kunjal Patel; Mary Paul; Diana Gibb; Rachel Vreeman; Elaine J Abrams; Rohan Hazra; Russell Van Dyke; Linda-Gail Bekker; Lynne Mofenson; Marissa Vicari; Shaffiq Essajee; Martina Penazzato; Gabriel Anabwani; Edith Q Mohapi; Peter N Kazembe; Makhosazana Hlatshwayo; Mwita Lumumba; Tessa Goetghebuer; Claire Thorne; Luisa Galli; Annemarie van Rossum; Carlo Giaquinto; Magdalena Marczynska; Laura Marques; Filipa Prata; Luminita Ene; Liubov Okhonskaia; Pablo Rojo; Claudia Fortuny; Lars Naver; Christoph Rudin; Sophie Le Coeur; Alla Volokha; Vanessa Rouzier; Regina Succi; Annette Sohn; Azar Kariminia; Andrew Edmonds; Patricia Lelo; Samuel Ayaya; Patricia Ongwen; Laura F Jefferys; Sam Phiri; Mwangelwa Mubiana-Mbewe; Shobna Sawry; Lorna Renner; Mariam Sylla; Mark J Abzug; Myron Levin; James Oleske; Miriam Chernoff; Shirley Traite; Murli Purswani; Ellen G Chadwick; Ali Judd; Valériane Leroy Journal: PLoS Med Date: 2018-03-01 Impact factor: 11.069
Authors: Wei Li A Koay; Sahera Dirajlal-Fargo; Matthew E Levy; Paige Kulie; Anne Monroe; Amanda D Castel; Natella Y Rakhmanina Journal: Open Forum Infect Dis Date: 2021-07-01 Impact factor: 3.835