title: Pubertal development in HIV-infected African children on first-line antiretroviral therapy.
abstract: OBJECTIVE
  To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation.
  
  
  METHODS
  Observational analysis within a randomized trial.
  
  
  METHODS
  Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories.
  
  
  RESULTS
  Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n = 582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P < 0.05) and menarche (P = 0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P < 0.05) in both sexes and pre-ART BMI-for-age in girls (P < 0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P < 0.01).
  
  
  CONCLUSIONS
  Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children.
authors.affiliation: aMRC Clinical Trials Unit at University College London, London, UK bJoint Clinical Research Centre cMakerere University College of Health Sciences, Kampala, Uganda dUniversity of Zimbabwe, Harare, Zimbabwe eMedical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS, Entebbe fPaediatric Infectious Diseases Clinic/Baylor - Uganda, Mulago Hospital, Kampala, Uganda gQueen Mary University of London, London, UK. *All the authors contributed equally to the writing of this article.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szubert
authors.forename: Victor
authors.initials: V
authors.lastname: Musiime
authors.forename: Mutsawashe
authors.initials: M
authors.lastname: Bwakura-Dangarembizi
authors.forename: Patricia
authors.initials: P
authors.lastname: Nahirya-Ntege
authors.forename: Adeodata
authors.initials: A
authors.lastname: Kekitiinwa
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Kusum
authors.initials: K
authors.lastname: Nathoo
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Prendergast
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D041923:Adolescent Development; D000886:Anthropometry / Q000379:methods; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy; D014454:Uganda; D015030:Zimbabwe; D016032:Randomized Controlled Trials as Topic
chemical_list: D044966:Anti-Retroviral Agents