Neurocognitive dysfunction in HIV-infected youth: investigating the relationship with immune activation.
HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth.



HIV-infected youth 8-26-years-old on cART with virological suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales. Soluble and cellular markers of T-lymphocyte and monocyte activation were measured by ELISA and flow cytometry, respectively.



45 HIV-infected subjects and 21 controls were enrolled. Markers of T-cell and monocyte activation were higher in the HIV-infected subjects compared to controls, but proportions of inflammatory and patrolling monocytes were similar. Although there were no significant differences in neurocognitive scores between the HIV-infected and control groups, scores were low-average for four of five testing domains for the HIV-infected subjects and average for all five in the controls, and % of HIV-infected subjects with scores classified as 'low average' or below was higher than in the controls. Variables most associated with neurocognitive performance among HIV-infected subjects included activated CD4+T-cells (% CD4+CD38+HLA-DR), monocyte activation (soluble CD14), HIV duration, age and sex.



HIV-infected youth on cART with virological suppression show subtle evidence of neurocognitive impairment compared to healthy controls, and increased immune activation appears to play a role. Additional studies are needed to develop strategic interventions beyond cART to potentially improve neurocognitive performance and/or minimize further impairment in this vulnerable population. ClinicalTrials.gov Identifier: NCT01523496.
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.|Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
Allison Ross
AR
Eckard
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Julia C
JC
Rosebush
Rainbow Babies & Children's Hospital and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Mary Ann
MA
O'Riordan
Department of Psychology, Emory University School of Medicine, Atlanta, GA, USA.
Chanda C
CC
Graves
Children's Healthcare of Atlanta, Atlanta, GA, USA.
Ashley
A
Alexander
Department of Psychology, Georgia State University, Atlanta, GA, USA.
Anita K
AK
Grover
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
S Thera
ST
Lee
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Jakob G
JG
Habib
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Joshua H
JH
Ruff
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.|Children's Healthcare of Atlanta, Atlanta, GA, USA.
Ann
A
Chahroudi
Rainbow Babies & Children's Hospital and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Grace A
GA
McComsey
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D002648:Child; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000209:etiology* / Q000523:psychology*; D003430:Cross-Sectional Studies; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007109:Immunity; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D000073216:Mental Status and Dementia Tests; D019965:Neurocognitive Disorders / Q000175:diagnosis / Q000209:etiology* / Q000523:psychology*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D015415:Biomarkers