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
Identifieur interne : 002A27 ( Main/Merge ); précédent : 002A26; suivant : 002A28Cognitive 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
Auteurs : Thanyawee Puthanakit [Thaïlande] ; Jintanat Ananworanich [Thaïlande, Pays-Bas, Australie] ; Saphonn Vonthanak [Cambodge] ; Pope Kosalaraksa [Thaïlande] ; Rawiwan Hansudewechakul [Thaïlande] ; Jasper Van Der Lugt [Thaïlande, Pays-Bas] ; Stephen J. Kerr [Thaïlande, Australie] ; Suparat Kanjanavanit [Thaïlande] ; Chaiwat Ngampiyaskul [Thaïlande] ; Jurai Wongsawat [Thaïlande] ; Wicharn Luesomboon [Thaïlande] ; Ung Vibol [Cambodge] ; Kanchana Pruksakaew [Thaïlande] ; Tulathip Suwarnlerk [Thaïlande] ; Tanakorn Apornpong [Thaïlande] ; Kattiya Ratanadilok [Thaïlande] ; Robert Paul [États-Unis] ; Lynne M. Mofenson [États-Unis] ; Lawrence Fox [États-Unis] ; Victor Valcour [Thaïlande, États-Unis] ; Pim Brouwers [États-Unis] ; Kiat Ruxrungtham [Thaïlande]Source :
- The Pediatric infectious disease journal [ 0891-3668 ] ; 2013.
Abstract
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 vs. deferred ART in the PREDICT Study. We now report neurodevelopmental outcomes.
284 HIV-infected Thai and Cambodian children aged 1–12 years with CD4 counts between 15–24% and no AIDS-defining illness were randomized to initiate ART at enrollment (“early”, n=139) or when CD4 count became <15% or a CDC C event developed (“deferred”, n=145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration (VMI), Purdue Pegboard, Color Trails and Child Behavioral Checklist (CBCL). Thai children (n=170) also completed Wechsler Intelligence Scale (IQ) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n=319).
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% vs. 24%, p<0.001) and a greater percentage of children with viral suppression (91% vs. 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 IQ, Beery VMI, Binet memory and CBCL
In HIV-infected children surviving beyond one year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15–24% vs. < 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.
Url:
DOI: 10.1097/INF.0b013e31827fb19d
PubMed: 23263176
PubMed Central: 3664246
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<author><name sortKey="Hansudewechakul, Rawiwan" sort="Hansudewechakul, Rawiwan" uniqKey="Hansudewechakul R" first="Rawiwan" last="Hansudewechakul">Rawiwan Hansudewechakul</name>
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<author><name sortKey="Suwarnlerk, Tulathip" sort="Suwarnlerk, Tulathip" uniqKey="Suwarnlerk T" first="Tulathip" last="Suwarnlerk">Tulathip Suwarnlerk</name>
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<author><name sortKey="Paul, Robert" sort="Paul, Robert" uniqKey="Paul R" first="Robert" last="Paul">Robert Paul</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Psychology, University of Missouri, St. Louis, MO</wicri:regionArea>
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<author><name sortKey="Mofenson, Lynne M" sort="Mofenson, Lynne M" uniqKey="Mofenson L" first="Lynne M." last="Mofenson">Lynne M. Mofenson</name>
<affiliation wicri:level="2"><nlm:aff id="A17"><italic>Eunice Kennedy Shriver</italic>
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
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<wicri:regionArea> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD</wicri:regionArea>
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<author><name sortKey="Fox, Lawrence" sort="Fox, Lawrence" uniqKey="Fox L" first="Lawrence" last="Fox">Lawrence Fox</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea>
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<author><name sortKey="Valcour, Victor" sort="Valcour, Victor" uniqKey="Valcour V" first="Victor" last="Valcour">Victor Valcour</name>
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<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
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<affiliation wicri:level="2"><nlm:aff id="A19">Memory and Aging Center, University of California at San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Memory and Aging Center, University of California at San Francisco, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
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<author><name sortKey="Brouwers, Pim" sort="Brouwers, Pim" uniqKey="Brouwers P" first="Pim" last="Brouwers">Pim Brouwers</name>
<affiliation wicri:level="2"><nlm:aff id="A20">National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>National Institute of Mental Health, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
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<author><name sortKey="Ruxrungtham, Kiat" sort="Ruxrungtham, Kiat" uniqKey="Ruxrungtham K" first="Kiat" last="Ruxrungtham">Kiat Ruxrungtham</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A2">Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand</nlm:aff>
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<country xml:lang="fr">Thaïlande</country>
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<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
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<affiliation wicri:level="3"><nlm:aff id="A8">The Amsterdam Institute of Global Health and Development, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Amsterdam Institute of Global Health and Development, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW</wicri:regionArea>
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<author><name sortKey="Vonthanak, Saphonn" sort="Vonthanak, Saphonn" uniqKey="Vonthanak S" first="Saphonn" last="Vonthanak">Saphonn Vonthanak</name>
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<country xml:lang="fr">Cambodge</country>
<wicri:regionArea>National Center for HIV/AIDS Dermatology and STDs, Phnom Penh</wicri:regionArea>
<wicri:noRegion>Phnom Penh</wicri:noRegion>
</affiliation>
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<author><name sortKey="Kosalaraksa, Pope" sort="Kosalaraksa, Pope" uniqKey="Kosalaraksa P" first="Pope" last="Kosalaraksa">Pope Kosalaraksa</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen</wicri:regionArea>
<wicri:noRegion>Khon Kaen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hansudewechakul, Rawiwan" sort="Hansudewechakul, Rawiwan" uniqKey="Hansudewechakul R" first="Rawiwan" last="Hansudewechakul">Rawiwan Hansudewechakul</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Chiangrai Prachanukroh Hospital, Chiang Rai</wicri:regionArea>
<wicri:noRegion>Chiang Rai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Lugt, Jasper" sort="Van Der Lugt, Jasper" uniqKey="Van Der Lugt J" first="Jasper" last="Van Der Lugt">Jasper Van Der Lugt</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A8">The Amsterdam Institute of Global Health and Development, Amsterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Amsterdam Institute of Global Health and Development, Amsterdam</wicri:regionArea>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kerr, Stephen J" sort="Kerr, Stephen J" uniqKey="Kerr S" first="Stephen J." last="Kerr">Stephen J. Kerr</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A9">The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW</wicri:regionArea>
<wicri:noRegion>NSW</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kanjanavanit, Suparat" sort="Kanjanavanit, Suparat" uniqKey="Kanjanavanit S" first="Suparat" last="Kanjanavanit">Suparat Kanjanavanit</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Nakornping Hospital, Chiang Mai, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Nakornping Hospital, Chiang Mai</wicri:regionArea>
<wicri:noRegion>Chiang Mai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ngampiyaskul, Chaiwat" sort="Ngampiyaskul, Chaiwat" uniqKey="Ngampiyaskul C" first="Chaiwat" last="Ngampiyaskul">Chaiwat Ngampiyaskul</name>
<affiliation wicri:level="1"><nlm:aff id="A11">Prapokklao Hospital, Chantaburi, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Prapokklao Hospital, Chantaburi</wicri:regionArea>
<wicri:noRegion>Chantaburi</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wongsawat, Jurai" sort="Wongsawat, Jurai" uniqKey="Wongsawat J" first="Jurai" last="Wongsawat">Jurai Wongsawat</name>
<affiliation wicri:level="1"><nlm:aff id="A12">Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Bamrasnaradura Infectious Diseases Institute, Nonthaburi</wicri:regionArea>
<wicri:noRegion>Nonthaburi</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Luesomboon, Wicharn" sort="Luesomboon, Wicharn" uniqKey="Luesomboon W" first="Wicharn" last="Luesomboon">Wicharn Luesomboon</name>
<affiliation wicri:level="1"><nlm:aff id="A13">Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Queen Savang Vadhana Memorial Hospital, Chonburi</wicri:regionArea>
<wicri:noRegion>Chonburi</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Vibol, Ung" sort="Vibol, Ung" uniqKey="Vibol U" first="Ung" last="Vibol">Ung Vibol</name>
<affiliation wicri:level="1"><nlm:aff id="A14">National Pediatric Hospital, Phnom Penh, Cambodia</nlm:aff>
<country xml:lang="fr">Cambodge</country>
<wicri:regionArea>National Pediatric Hospital, Phnom Penh</wicri:regionArea>
<wicri:noRegion>Phnom Penh</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pruksakaew, Kanchana" sort="Pruksakaew, Kanchana" uniqKey="Pruksakaew K" first="Kanchana" last="Pruksakaew">Kanchana Pruksakaew</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Suwarnlerk, Tulathip" sort="Suwarnlerk, Tulathip" uniqKey="Suwarnlerk T" first="Tulathip" last="Suwarnlerk">Tulathip Suwarnlerk</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Apornpong, Tanakorn" sort="Apornpong, Tanakorn" uniqKey="Apornpong T" first="Tanakorn" last="Apornpong">Tanakorn Apornpong</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ratanadilok, Kattiya" sort="Ratanadilok, Kattiya" uniqKey="Ratanadilok K" first="Kattiya" last="Ratanadilok">Kattiya Ratanadilok</name>
<affiliation wicri:level="1"><nlm:aff id="A15">Department of Juvenile Observation and Protection, Ministry of Justice, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Department of Juvenile Observation and Protection, Ministry of Justice</wicri:regionArea>
<wicri:noRegion>Ministry of Justice</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Paul, Robert" sort="Paul, Robert" uniqKey="Paul R" first="Robert" last="Paul">Robert Paul</name>
<affiliation wicri:level="2"><nlm:aff id="A16">Department of Psychology, University of Missouri, St. Louis, MO, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Psychology, University of Missouri, St. Louis, MO</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mofenson, Lynne M" sort="Mofenson, Lynne M" uniqKey="Mofenson L" first="Lynne M." last="Mofenson">Lynne M. Mofenson</name>
<affiliation wicri:level="2"><nlm:aff id="A17"><italic>Eunice Kennedy Shriver</italic>
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fox, Lawrence" sort="Fox, Lawrence" uniqKey="Fox L" first="Lawrence" last="Fox">Lawrence Fox</name>
<affiliation wicri:level="2"><nlm:aff id="A18">Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Valcour, Victor" sort="Valcour, Victor" uniqKey="Valcour V" first="Victor" last="Valcour">Victor Valcour</name>
<affiliation wicri:level="1"><nlm:aff id="A4">SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A19">Memory and Aging Center, University of California at San Francisco, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Memory and Aging Center, University of California at San Francisco, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Brouwers, Pim" sort="Brouwers, Pim" uniqKey="Brouwers P" first="Pim" last="Brouwers">Pim Brouwers</name>
<affiliation wicri:level="2"><nlm:aff id="A20">National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>National Institute of Mental Health, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ruxrungtham, Kiat" sort="Ruxrungtham, Kiat" uniqKey="Ruxrungtham K" first="Kiat" last="Ruxrungtham">Kiat Ruxrungtham</name>
<affiliation wicri:level="1"><nlm:aff id="A1">HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand</nlm:aff>
<country xml:lang="fr">Thaïlande</country>
<wicri:regionArea>Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok</wicri:regionArea>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">The Pediatric infectious disease journal</title>
<idno type="ISSN">0891-3668</idno>
<idno type="eISSN">1532-0987</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">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 vs. deferred ART in the PREDICT Study. We now report neurodevelopmental outcomes.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">284 HIV-infected Thai and Cambodian children aged 1–12 years with CD4 counts between 15–24% and no AIDS-defining illness were randomized to initiate ART at enrollment (“early”, n=139) or when CD4 count became <15% or a CDC C event developed (“deferred”, n=145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration (VMI), Purdue Pegboard, Color Trails and Child Behavioral Checklist (CBCL). Thai children (n=170) also completed Wechsler Intelligence Scale (IQ) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n=319).</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">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% vs. 24%, p<0.001) and a greater percentage of children with viral suppression (91% vs. 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 IQ, Beery VMI, Binet memory and CBCL</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">In HIV-infected children surviving beyond one year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15–24% vs. < 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.</p>
</sec>
</div>
</front>
</TEI>
</record>
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