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)
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Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
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Brouwers, Pim
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Medland, Sarah E; Jahanshad, Neda; Neale, Benjamin M et al. (2014) Whole-genome analyses of whole-brain data: working within an expanded search space. Nat Neurosci 17:791-800
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
Thompson, Paul M; Ge, Tian; Glahn, David C et al. (2013) Genetics of the connectome. Neuroimage 80:475-88
Chokephaibulkit, Kulkanya; Saksawad, Rachanee; Bunupuradah, Torsak et al. (2013) Prevalence of vitamin D deficiency among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy. Pediatr Infect Dis J 32:1237-9
Bunupuradah, Torsak; Puthanakit, Thanyawee; Kosalaraksa, Pope et al. (2012) Poor quality of life among untreated Thai and Cambodian children without severe HIV symptoms. AIDS Care 24:30-8
Thompson, Paul M; Vinters, Harry V (2012) Pathologic lesions in neurodegenerative diseases. Prog Mol Biol Transl Sci 107:1-40