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
Thanyawee Puthanakit, Jintanat Ananworanich, Saphonn Vonthanak, Pope Kosalaraksa, Rawiwan Hansudewechakul, Jasper van der Lugt, Stephen J Kerr, Suparat Kanjanavanit, Chaiwat Ngampiyaskul, Jurai Wongsawat, Wicharn Luesomboon, Ung Vibol, Kanchana Pruksakaew, Tulathip Suwarnlerk, Tanakorn Apornpong, Kattiya Ratanadilok, Robert Paul, Lynne M Mofenson, Lawrence Fox, Victor Valcour, Pim Brouwers, Kiat Ruxrungtham, PREDICT Study Group, Praphan Phanuphak, David A Cooper, John Kaldor, Mean Chhi Vun, Saphonn Vonthanak, Kiat Ruxrungtham, Carlo Giaquinto, Mark Cotton, Rangsima Lolekha, Virat Sirisanthana, Kulkanya Chokephaibulkit, Piyarat Suntarattiwong, Paul Volberding, Shrikant Bangdiwala, Kruy Lim, N M Samuel, David Schoenfeld, Annette Sohn, Suniti Solomon, Panpit Suwangool, Ruotao Wang, Fujie Zhang, Laurie Zoloth, Dennis O Dixon, Lawrence Fox, Akinlolu O Ojumu, Jane E Bupp, Michael Ussery, Neal T Wetherall, Pim Brouwers, Lynne M Mofenson, Macaya Douoguih, Eva Petrakova, Matthew Law, William T Shearer, Victor Valcour, Rober Paul, Kovit Pattanapanyasat, Natthaga Sakulploy, Janet M McNicholl, Chutima Saisaengjan, Kattiya Rattanadilok, Wendy Snowden, Navdeep K Thoofer, Manuel Distel, Annette S Meints, Adawan Methasate, Matei Popescu, Aeumporn Srigritsanapol, Suchai Kitsiripornchai, Thanyawee Puthanakit, Jintanat Ananworanich, Saphonn Vonthanak, Pope Kosalaraksa, Rawiwan Hansudewechakul, Jasper van der Lugt, Stephen J Kerr, Suparat Kanjanavanit, Chaiwat Ngampiyaskul, Jurai Wongsawat, Wicharn Luesomboon, Ung Vibol, Kanchana Pruksakaew, Tulathip Suwarnlerk, Tanakorn Apornpong, Kattiya Ratanadilok, Robert Paul, Lynne M Mofenson, Lawrence Fox, Victor Valcour, Pim Brouwers, Kiat Ruxrungtham, PREDICT Study Group, Praphan Phanuphak, David A Cooper, John Kaldor, Mean Chhi Vun, Saphonn Vonthanak, Kiat Ruxrungtham, Carlo Giaquinto, Mark Cotton, Rangsima Lolekha, Virat Sirisanthana, Kulkanya Chokephaibulkit, Piyarat Suntarattiwong, Paul Volberding, Shrikant Bangdiwala, Kruy Lim, N M Samuel, David Schoenfeld, Annette Sohn, Suniti Solomon, Panpit Suwangool, Ruotao Wang, Fujie Zhang, Laurie Zoloth, Dennis O Dixon, Lawrence Fox, Akinlolu O Ojumu, Jane E Bupp, Michael Ussery, Neal T Wetherall, Pim Brouwers, Lynne M Mofenson, Macaya Douoguih, Eva Petrakova, Matthew Law, William T Shearer, Victor Valcour, Rober Paul, Kovit Pattanapanyasat, Natthaga Sakulploy, Janet M McNicholl, Chutima Saisaengjan, Kattiya Rattanadilok, Wendy Snowden, Navdeep K Thoofer, Manuel Distel, Annette S Meints, Adawan Methasate, Matei Popescu, Aeumporn Srigritsanapol, Suchai Kitsiripornchai
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.
Conflict of interest statement
Conflict of interest of authors
TP has received speaker honoraria from Abbott. JA has received consultation or speaker honoraria from ViiV Health Care and Abbott. KR has been received consultation or speaker honoraria from ViiV Health Care and Abbott. Other authors reported no conflict of interest.
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Source: PubMed