title: Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe.
abstract: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
authors.forename: Michael
authors.initials: M
authors.lastname: Schomaker
authors.affiliation: Inserm, U1027, Université Paul Sabatier Toulouse 3 Toulouse, France.
authors.forename: Valeriane
authors.initials: V
authors.lastname: Leroy
authors.affiliation: Children's Hospital/UMCU, Department of Infectious Diseases, Utrecht, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Wolfs
authors.affiliation: Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa.|Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Karl-Günter
authors.initials: KG
authors.lastname: Technau
authors.affiliation: University of Ghana Medical School, Accra, Ghana.
authors.forename: Lorna
authors.initials: L
authors.lastname: Renner
authors.affiliation: MRC Clinical Trials Unit, University College London, London, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Judd
authors.affiliation: University of the Witwatersrand, Wits Reproductive Health and HIV Institute, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.
authors.forename: Shobna
authors.initials: S
authors.lastname: Sawry
authors.affiliation: Félix Houphouët Boigny University Hospital, Abidjan, Côte d'Ivoire.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Amorissani-Folquet
authors.affiliation: Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.affiliation: Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.|School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.|Centre for the AIDS Programme of Research in South Africa - CAPRISA, University of KwaZulu-Natal, Congella, South Africa.
authors.forename: Frank
authors.initials: F
authors.lastname: Tanser
authors.affiliation: Yopougon University Hospital, Abidjan, Côte d'Ivoire.
authors.forename: François
authors.initials: F
authors.lastname: Eboua
authors.affiliation: Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Navarro
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Cleophas
authors.initials: C
authors.lastname: Chimbetete
authors.affiliation: MTCT-Plus Center, Abidjan, Côte d'Ivoire.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Amani-Bosse
authors.affiliation: Centre de recherche en épidémiologie et santé des populations, 1018 Inserm, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Warszawski
authors.affiliation: Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi.
authors.forename: Sam
authors.initials: S
authors.lastname: Phiri
authors.affiliation: Centre de Prise en Charge de Recherche et de Formation Enfants, Abidjan, Côte d'Ivoire.
authors.forename: Sylvie
authors.initials: S
authors.lastname: N'Gbeche
authors.affiliation: Médecins Sans Frontiéres South Africa, Cape Town, South Africa.
authors.forename: Vivian
authors.initials: V
authors.lastname: Cox
authors.affiliation: Charles de Gaulle University Hospital, Ouagadougou, Burkina Faso.
authors.forename: Fla
authors.initials: F
authors.lastname: Koueta
authors.affiliation: Sinikithemba Clinic, McCord Hospital, Durban, South Africa.
authors.forename: Janet
authors.initials: J
authors.lastname: Giddy
authors.affiliation: Albert Royer Hospital, Dakar, Senegal.
authors.forename: Haby
authors.initials: H
authors.lastname: Sygnaté-Sy
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Dorthe
authors.initials: D
authors.lastname: Raben
authors.affiliation: University of Bordeaux Bordeaux, ISPED, Centre INSERM U1219-Bordeaux Population Health, F-33000 Bordeaux, France.|INSERM, ISPED, Centre INSERM U1219-Bordeaux Population Health, F-33000 Bordeaux, France.|CHU de Bordeaux, Pôle de santé publique, Service d information médicale, F-33000 Bordeaux, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.affiliation: Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000353:Africa, Southern / Q000453:epidemiology; D000354:Africa, Western / Q000453:epidemiology; D017677:Age Distribution; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D001835:Body Weight; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D003710:Demography; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D017678:Sex Distribution; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents
keywords: Antiretroviral treatment; causal inference; g-formula; paediatrics