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) alsocompleted 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.
RCT Entities:
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-uninfectedchildren (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-infectedchildren performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist. CONCLUSIONS: In HIV-infectedchildren 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-uninfectedchildren. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.
Authors: L G Epstein; L R Sharer; J M Oleske; E M Connor; J Goudsmit; L Bagdon; M Robert-Guroff; M R Koenigsberger Journal: Pediatrics Date: 1986-10 Impact factor: 7.124
Authors: Molly L Nozyce; Sophia S Lee; Andrew Wiznia; Sharon Nachman; Lynne M Mofenson; Mary E Smith; Ram Yogev; Kenneth McIntosh; Kenneth Stanley; Stephen Pelton Journal: Pediatrics Date: 2006-03 Impact factor: 7.124
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: Sally Grantham-McGregor; Yin Bun Cheung; Santiago Cueto; Paul Glewwe; Linda Richter; Barbara Strupp Journal: Lancet Date: 2007-01-06 Impact factor: 79.321
Authors: Heather Carryl; Melanie Swang; Jerome Lawrence; Kimberly Curtis; Herman Kamboj; Koen K A Van Rompay; Kristina De Paris; Mark W Burke Journal: ACS Chem Neurosci Date: 2015-06-19 Impact factor: 4.418
Authors: Sarah F Benki-Nugent; Ira Martopullo; Tony Laboso; Nancy Tamasha; Dalton C Wamalwa; Kenneth Tapia; Agnes Langat; Elizabeth Maleche-Obimbo; Christina M Marra; Paul Bangirana; Michael J Boivin; Grace C John-Stewart Journal: J Acquir Immune Defic Syndr Date: 2019-05-01 Impact factor: 3.731
Authors: Heena Brahmbhatt; Michael Boivin; Victor Ssempijja; Godfrey Kigozi; Joseph Kagaayi; David Serwadda; Ronald H Gray Journal: J Acquir Immune Defic Syndr Date: 2014-11-01 Impact factor: 3.731
Authors: Nicole Phillips; Taryn Amos; Caroline Kuo; Jacqueline Hoare; Jonathan Ipser; Kevin G F Thomas; Dan J Stein Journal: Pediatrics Date: 2016-10-11 Impact factor: 7.124