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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

Puthanakit, Thanyawee MD*†; Ananworanich, Jintanat MD, PhD*‡§ †† ‡‡; Vonthanak, Saphonn MD, PhD; Kosalaraksa, Pope MD; Hansudewechakul, Rawiwan MD**; van der Lugt, Jasper MD, PhD*††; Kerr, Stephen J. PhD*‡‡; Kanjanavanit, Suparat MD§§; Ngampiyaskul, Chaiwat MD¶¶; Wongsawat, Jurai MD‖‖; Luesomboon, Wicharn MD***; Vibol, Ung MD†††; Pruksakaew, Kanchana BSc*; Suwarnlerk, Tulathip BNS*; Apornpong, Tanakorn MSc*; Ratanadilok, Kattiya PhD‡‡‡; Paul, Robert PhD§§§; Mofenson, Lynne M. MD¶¶¶; Fox, Lawrence MD, PhD‖‖‖; Valcour, Victor MD§ ****; Brouwers, Pim PhD††††; Ruxrungtham, Kiat MD, MSc*‡; on behalf of the PREDICT Study Group

Pediatric Infectious Disease Journal: May 2013 - Volume 32 - Issue 5 - p 501–508
doi: 10.1097/INF.0b013e31827fb19d
HIV Reports

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.

From the *HIV-NAT, The Thai Red Cross AIDS Research Centre; Departments of Pediatrics and Medicine, Faculty of Medicine, Chulalongkorn University; §SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; National Center for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen; **Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ††The Amsterdam Institute of Global Health and Development, Amsterdam, The Netherlands; ‡‡The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia; §§Nakornping Hospital, Chiang Mai; ¶¶Prapokklao Hospital, Chantaburi; ‖‖Bamrasnaradura Infectious Diseases Institute, Nonthaburi; ***Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand; †††National Pediatric Hospital, Phnom Penh, Cambodia; ‡‡‡Department of Juvenile Observation and Protection, Ministry of Justice, Thailand; §§§Department of Psychology, University of Missouri, St. Louis, MO; ¶¶¶Eunice Kennedy Shriver National Institute of Child Health and Human Development; ‖‖‖Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; ****Memory and Aging Center, University of California at San Francisco, CA; and ††††National Institute of Mental Health, National Institutes of Health, Bethesda, MD.

This work has been presented in part at the 19th Conference on Retroviruses and Opportunistic. March 5–8, 2012, Seattle (Abstract 24).

The work was supported by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health through the Comprehensive International Program of Research on AIDS Network (U19 AI53741); cofunded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health. The antiretroviral was drug supported by ViiV Health Care/GlaxoSmithKline, Boehringer-Ingelheim, Merck, Abbott and Roche. The views in this report do not necessary reflect the views of the National Institutes of Health or US Department of Health and Human Services. K.R. has received support through grants HR1161A from the National Research University Project of CHE and the Ratchadaphiseksomphot Endowment Fund, Thailand; the Professional Researcher Strengthen Grant from the National Science and Technology Development Agency, BIOTEC, and the Senior Researcher Scholar from Thai Research Fund, Thailand.

T.P. has received speaker honoraria from Abbott. J.A. has received consultation or speaker honoraria from ViiV Health Care and Abbott. K.R. has been received consultation or speaker honoraria from ViiV Health Care and Abbott. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence and reprint request: Jintanat Ananworanich, MD, PhD, HIV-NAT, The Thai Red Cross AIDS Research Center, 104 Rajdumri Road, Pathumwan, Bangkok 10330 Thailand. E-mail: Jintanat.A@hivnat.org.

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