title: Correlates of age at attainment of developmental milestones in HIV-infected infants receiving early antiretroviral therapy.
abstract: BACKGROUND
  Infant HIV-1 infection is associated with impaired neurologic and motor development. Antiretroviral therapy (ART) has the potential to improve developmental outcomes but the relative contributions of pre-ART disease status, growth, treatment regimen and ART response during infancy are unknown.
  
  
  METHODS
  Kenyan ART-naive infants <5-months old initiated ART and had monthly assessment of age of full neck control, unsupported walking and monosyllabic speech during 24 months of follow-up. Pre-ART and post-ART correlates of age at milestone attainment were evaluated using t tests or multivariate linear regression.
  
  
  RESULTS
  Among 99 infants, pre-ART correlates of later milestone attainment included: underweight and stunted (neck control, walking and speech, all P values <0.05), missed prevention of mother-to-child transmission (P = 0.04) (neck control), previous hospitalization, World Health Organization (WHO) Stage III/IV, low CD4 count, and wasting (speech and walking, all P values <0.05), and low maternal CD4 (speech, P = 0.04). Infants initiated ART at a median of 14 days following enrollment. Infants receiving nevirapinevs lopinavir/ritonavir-based ART attained later speech (18.1 vs. 15.5 months, P = 0.003) [corrected]. Adjusting for pre-ART level, lower 6-month gain in CD4% was associated with later walking (0.18 months earlier per unit increase in CD4%; P = 0.004) and speech (0.12 months earlier per unit increase in CD4%; P = 0.05), and lower 6-month gains in weight-for-age (P = 0.009), height-for-age (P = 0.03) and weight-for-height (P = 0.02) were associated with later walking.
  
  
  CONCLUSIONS
  In HIV-infected infants, compromised pre-ART immune and growth status, poor post-ART immune and growth responses, and use of nevirapine- vs. lopinavir/ritonavir-based ART were each associated with later milestone attainment [corrected]. The long-term consequences of these delays are unknown.
authors.affiliation: From the Departments of *Global Health, and †Epidemiology, University of Washington, Seattle; and ‡Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
authors.forename: Sarah
authors.initials: S
authors.lastname: Benki-Nugent
authors.forename: Christal
authors.initials: C
authors.lastname: Eshelman
authors.forename: Dalton
authors.initials: D
authors.lastname: Wamalwa
authors.forename: Agnes
authors.initials: A
authors.lastname: Langat
authors.forename: Ken
authors.initials: K
authors.lastname: Tapia
authors.forename: Helen Moraa
authors.initials: HM
authors.lastname: Okinyi
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002657:Child Development; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007630:Kenya; D061466:Lopinavir / Q000627:therapeutic use; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use
chemical_list: D044966:Anti-Retroviral Agents; D061466:Lopinavir; D019829:Nevirapine; D019438:Ritonavir