TY - JOUR
T1 - Deformed Subcortical Structures Are Related to Past HIV Disease Severity in Youth With Perinatally Acquired HIV Infection
AU - for the Pediatric HIV/AIDS Cohort Study (PHACS)
AU - Lewis-de los Angeles, C. Paula
AU - Alpert, Kathryn I.
AU - Williams, Paige L.
AU - Malee, Kathleen
AU - Huo, Yanling
AU - Csernansky, John G.
AU - Yogev, Ram
AU - Van Dyke, Russell B.
AU - Sowell, Elizabeth R.
AU - Wang, Lei
N1 - Funding Information:
Financial support. The PHACS was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism through cooperative agreements with the Harvard T. H. Chan School of Public Health (Grant HD052102) and the Tulane University School of Medicine (Grant HD052104). Data-management services were provided by Frontier Science and Technology Research Foundation and regulatory services and logistical support were provided byWestat, Inc. The neuroimaging study was also supported by the Northwestern University Training Program in the Neuroscience of Human Cognition (Grant T32 NS047987) and the Northwestern University Medical Scientist Training Program (Grant T32 GM008152).
Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Background. Combination antiretroviral therapy has led to increased survival among youth with perinatally acquired HIV (PHIV). However, cognitive deficits continue to be common. Histopathological studies in adults have found HIV concentrated in subcortical structures, which are involved in sensory processing, movement, and higher-order cognition that emerges with development. Methods. We conducted magnetic resonance imaging and cognitive testing in 40 youth with PHIV at one site of the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study. We collected HIV disease-severity measures and substance-use reports. Subcortical volume and shape deformation were generated with FreeSurfer- Initiated Large Deformation Diffeomorphic Metric Mapping. Inward shape deformation was defined as negative displacement.We evaluated associations of subcortical shape deformation with past HIV severity after adjustment for sex, age at neuroimaging, age at HIV severity marker, and substance use. We examined associations between subcortical deformation and cognitive function. Results. Negative correlations between shape deformation and peak HIV viral load (VL) were found in clusters in the caudate tail, globus pallidus, lateral putamen, and anterior and medial thalamus. Positive correlations between shape deformation and nadir CD4-positive T-lymphocyte percentage (CD4%) were found in clusters in the medial and posterior thalamus. Inward deformation in caudate and thalamic clusters correlated with worse cognition. Conclusions. Youth with PHIV have demonstrable subcortical shape deformation related to past HIV severity and cognition; inward deformation was associated with higher peak VL, lower nadir CD4%, and worse cognition. Identifying subcortical deformation may inform clinical practice for early intervention to help improve cognitive outcomes and assess the neuroefficacy of combination antiretroviral therapy in youth with PHIV.
AB - Background. Combination antiretroviral therapy has led to increased survival among youth with perinatally acquired HIV (PHIV). However, cognitive deficits continue to be common. Histopathological studies in adults have found HIV concentrated in subcortical structures, which are involved in sensory processing, movement, and higher-order cognition that emerges with development. Methods. We conducted magnetic resonance imaging and cognitive testing in 40 youth with PHIV at one site of the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study. We collected HIV disease-severity measures and substance-use reports. Subcortical volume and shape deformation were generated with FreeSurfer- Initiated Large Deformation Diffeomorphic Metric Mapping. Inward shape deformation was defined as negative displacement.We evaluated associations of subcortical shape deformation with past HIV severity after adjustment for sex, age at neuroimaging, age at HIV severity marker, and substance use. We examined associations between subcortical deformation and cognitive function. Results. Negative correlations between shape deformation and peak HIV viral load (VL) were found in clusters in the caudate tail, globus pallidus, lateral putamen, and anterior and medial thalamus. Positive correlations between shape deformation and nadir CD4-positive T-lymphocyte percentage (CD4%) were found in clusters in the medial and posterior thalamus. Inward deformation in caudate and thalamic clusters correlated with worse cognition. Conclusions. Youth with PHIV have demonstrable subcortical shape deformation related to past HIV severity and cognition; inward deformation was associated with higher peak VL, lower nadir CD4%, and worse cognition. Identifying subcortical deformation may inform clinical practice for early intervention to help improve cognitive outcomes and assess the neuroefficacy of combination antiretroviral therapy in youth with PHIV.
KW - Adolescence
KW - Neuroimaging
KW - Perinatally acquired HIV
KW - Subcortical
KW - Viral load
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U2 - 10.1093/jpids/piw051
DO - 10.1093/jpids/piw051
M3 - Article
C2 - 27856671
AN - SCOPUS:85005949128
VL - 5
SP - S6-S14
JO - Journal of the Pediatric Infectious Diseases Society
JF - Journal of the Pediatric Infectious Diseases Society
SN - 2048-7207
ER -
