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Deformed Subcortical Structures Are Related to Past HIV Disease Severity in Youth With Perinatally Acquired HIV Infection.

ABSTRACT: 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.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.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.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.

SUBMITTER: Lewis-de Los Angeles CP

PROVIDER: S-EPMC5181545 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

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Deformed Subcortical Structures Are Related to Past HIV Disease Severity in Youth With Perinatally Acquired HIV Infection.

Lewis-de Los Angeles C Paula CP Alpert Kathryn I KI Williams Paige L PL Malee Kathleen K Huo Yanling Y Csernansky John G JG Yogev Ram R Van Dyke Russell B RB Sowell Elizabeth R ER Wang Lei L

Journal of the Pediatric Infectious Diseases Society 20161201 suppl 1

<h4>Background</h4>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.<h4>Methods</h4>We conducted magnetic resonance imaging and cognitive testing in 40 youth with PHIV at one site of ...[more]

PMID: 27856671

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Project description:OBJECTIVE:To identify factors associated with nonadherence and unsuppressed viral load across adolescence among youth with perinatally acquired HIV. DESIGN:Longitudinal study at 15 US clinical sites. METHODS:Self-reported antiretroviral medication nonadherence (any missed dose, past week) and unsuppressed viral load (HIV RNA?>?400 copies/ml) were assessed annually. Individual, caregiver, social, and structural factors associated with nonadherence and unsuppressed viral load were identified by age (years): 8-11 (preadolescence), 12-14 (early adolescence), 15-17 (middle adolescence), and 18-22 (late adolescence/young adulthood), utilizing multivariable generalized linear mixed effects models. RESULTS:During a median 3.3-year follow-up, 381 youth with perinatally acquired HIV contributed viral load measurements and 379 completed 1190 adherence evaluations. From preadolescence to late adolescence/young adulthood, prevalence of nonadherence increased from 31 to 50% (P?<?0.001); prevalence of unsuppressed viral load increased from 16 to 40% (P?<?0.001). In adjusted analyses, in pre, middle, and late adolescence/young adulthood, perceived antiretroviral side effects were associated with nonadherence. Additional factors associated with nonadherence included: in preadolescence, using a buddy system (as an adherence reminder); in early adolescence, identifying as black, using buddy system; in middle adolescence, CD4% less than 15%, unmarried caregiver, indirect exposure to violence, stigma/fear of inadvertent disclosure, stressful life events. Associations with unsuppressed viral load included: in early adolescence, youth unawareness of HIV status, lower income; in middle adolescence, perceived antiretroviral side effects, lower income; in late adolescence/young adulthood, distressing physical symptoms, and perceived antiretroviral side effects. CONCLUSION:Prevalence of nonadherence and unsuppressed viral load increased with age. Associated factors varied across adolescence. Recognition of age-specific factors is important when considering strategies to support adherence.

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Deformed Subcortical Structures Are Related to Past HIV Disease Severity in Youth With Perinatally Acquired HIV Infection.

Publications

Deformed Subcortical Structures Are Related to Past HIV Disease Severity in Youth With Perinatally Acquired HIV Infection.

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