title: Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study.
abstract: BACKGROUND
  We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes.
  
  
  METHODS
  Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319).
  
  
  RESULTS
  At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist.
  
  
  CONCLUSIONS
  In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.
authors.affiliation: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Saphonn
authors.initials: S
authors.lastname: Vonthanak
authors.forename: Pope
authors.initials: P
authors.lastname: Kosalaraksa
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Hansudewechakul
authors.forename: Jasper
authors.initials: J
authors.lastname: van der Lugt
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Suparat
authors.initials: S
authors.lastname: Kanjanavanit
authors.forename: Chaiwat
authors.initials: C
authors.lastname: Ngampiyaskul
authors.forename: Jurai
authors.initials: J
authors.lastname: Wongsawat
authors.forename: Wicharn
authors.initials: W
authors.lastname: Luesomboon
authors.forename: Ung
authors.initials: U
authors.lastname: Vibol
authors.forename: Kanchana
authors.initials: K
authors.lastname: Pruksakaew
authors.forename: Tulathip
authors.initials: T
authors.lastname: Suwarnlerk
authors.forename: Tanakorn
authors.initials: T
authors.lastname: Apornpong
authors.forename: Kattiya
authors.initials: K
authors.lastname: Ratanadilok
authors.forename: Robert
authors.initials: R
authors.lastname: Paul
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fox
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.forename: Pim
authors.initials: P
authors.lastname: Brouwers
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D060825:Cognitive Dysfunction / Q000821:virology*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D007223:Infant; D007361:Intelligence Tests; D008297:Male; D013785:Thailand; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents