There are 2.5 million children living the HIV/AIDS worldwide. Most live in resource- limited settings. Treatment guidelines for children are often based on findings in adults and seldom assembled from studies employing a randomized design. This rationale led the NIH to initiate the PREDICT study underway in Thailand and Cambodia. PREDICT uses a randomized design to determine the optimal timing of antiretroviral initiation in children. International guidelines for ART initiation in children older than 12 months continue to recommend deferring therapy until symptomatic disease or immune compromise occurs, despite studies in younger infants (CHER trial) identifying a benefit for early treatment. Treatment outcomes for older children are needed and neurodevelopmental outcomes could critically inform guidelines. This proposal will add robust neurodevelopmental and imaging outcomes to PREDICT. This work will extend our current limited evaluation of neurodevelopmental outcomes to determine if differences in long-term neuropsychological and neurological outcomes exist in relation to deferring antiretroviral therapy. We will also enroll needed HIV-negative comparative groups of HIV-exposed and unexposed children. Since microencephaly is a common manifestation of HIV in children, volumetric analyses may be most informative. Should the primary findings from PREDICT fail to identify differences by randomized group (immediate compared to deferred therapy), findings from the proposed work may have an enormous impact by informing treatment guidelines worldwide.

Public Health Relevance

HIV treatment guidelines for children are based on incomplete evidence. Neurodevelopmental outcomes may critically inform these guidelines. The proposed work will determine the brain impact of deferring antiretroviral therapy until there is immunosuppression, as currently recommended by WHO guidelines. Our findings may have an enormous impact on worldwide treatment recommendations.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Brouwers, Pim
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Paul, Robert; Apornpong, Tanakorn; Prasitsuebsai, Wasana et al. (2018) Cognition, Emotional Health, and Immunological Markers in Children With Long-Term Nonprogressive HIV. J Acquir Immune Defic Syndr 77:417-426
Paul, Robert; Prasitsuebsai, Wasana; Jahanshad, Neda et al. (2018) Structural Neuroimaging and Neuropsychologic Signatures in Children With Vertically Acquired HIV. Pediatr Infect Dis J 37:662-668
Zhang, Guohao; Kochunov, Peter; Hong, Elliot et al. (2017) ENIGMA-Viewer: interactive visualization strategies for conveying effect sizes in meta-analysis. BMC Bioinformatics 18:253
Brouwer, Rachel M; Panizzon, Matthew S; Glahn, David C et al. (2017) Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group. Hum Brain Mapp 38:4444-4458
Adams, Hieab H H (see original citation for additional authors) (2016) Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat Neurosci 19:1569-1582
Franke, Barbara; Stein, Jason L; Ripke, Stephan et al. (2016) Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nat Neurosci 19:420-431
Thompson, Paul M; Jahanshad, Neda (2015) Novel Neuroimaging Methods to Understand How HIV Affects the Brain. Curr HIV/AIDS Rep 12:289-98
Jahanshad, Neda; Couture, Marie-Claude; Prasitsuebsai, Wasana et al. (2015) Brain Imaging and Neurodevelopment in HIV-uninfected Thai Children Born to HIV-infected Mothers. Pediatr Infect Dis J 34:e211-6
Madsen, Sarah K; Zai, Alex; Pirnia, Tara et al. (2015) Cortical thickness and brain volumetric analysis in body dysmorphic disorder. Psychiatry Res 232:115-22
Kerr, Stephen J; Puthanakit, Thanyawee; Vibol, Ung et al. (2014) Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV. AIDS Care 26:1327-35

Showing the most recent 10 out of 21 publications