Colleen L Schneider1, Sarah Mohajeri-Moghaddam2, Esau G Mbewe3, Pelekelo P Kabundula3, Owen Dean4, Alexandra Buda4, Michael J Potchen5, Sylvia Mwanza-Kabaghe3, Deanna Saylor6, Heather R Adams7, Gretchen L Birbeck8, David R Bearden9. 1. Medical Scientist Training Program, University of Rochester School of Medicine and Dentistry, Rochester, New York; Department of Brain and Cognitive Science, University of Rochester, Rochester, New York; Department of Psychology, Carnegie Mellon University, Pittsburgh, Pennsylvania; University of Rochester School of Medicine and Dentistry, Rochester, New York. 2. Department of Radiology, University of California at Los Angeles, Los Angeles, California. 3. Department of Educational Psychology, Sociology and Special Education, The University of Zambia, Lusaka, Zambia. 4. University of Rochester School of Medicine and Dentistry, Rochester, New York. 5. Department of Radiology, University of Rochester Medical Center, Rochester, New York; Department of Radiology, Lusaka Apex Medical University, Lusaka, Zambia. 6. Department of Neurology, Johns Hopkins University, Baltimore, Maryland; Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia; Zambian Institute for Neurological Care, Research, and Education, Lusaka, Zambia. 7. Division of Child Neurology, Department of Neurology, University of Rochester Medical Center, Rochester, New York. 8. Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia; Zambian Institute for Neurological Care, Research, and Education, Lusaka, Zambia; Division of Epilepsy, Department of Neurology, University of Rochester Medical Center, Rochester, New York; University Teaching Hospital Children's Hospital, Lusaka, Zambia. 9. Department of Educational Psychology, Sociology and Special Education, The University of Zambia, Lusaka, Zambia; Zambian Institute for Neurological Care, Research, and Education, Lusaka, Zambia; Division of Child Neurology, Department of Neurology, University of Rochester Medical Center, Rochester, New York. Electronic address: David_bearden@urmc.rochester.edu.
Abstract
BACKGROUND: High rates of cerebrovascular disease (CVD) have previously been described in pediatric human immunodeficiency virus (HIV). However, little is known about pediatric CVD in the era of antiretroviral therapy or about the contribution of CVD to HIV-associated neurocognitive disorders. METHODS: We completed a neuroimaging substudy of the HIV-Associated Neurocognitive Disorders in Zambia study, a prospective cohort study of neurocognitive complications of pediatric HIV. Brain magnetic resonance imaging (1.5 T) was acquired for 34 HIV+ children on antiretroviral therapy and 17 HIV-exposed uninfected children (aged eight to 17 years). Demographics, medical history, neurological examination, and neuropsychologic testing results were collected. Two neuroradiologists, unaware of HIV status and clinical course, read the scans. RESULTS: CVD was identified in seven of 34 children with HIV (HIV+ CVD+) and no HIV-exposed uninfected children (21% vs 0%, P = 0.05). Three participants had white matter changes suggestive of small vessel disease, four had infarcts, and two had evidence of intracranial artery stenosis. Age of antiretroviral therapy initiation and exposure to protease inhibitors or efavirenz was not significantly different between children with and without CVD. HIV+ CVD+ children had significantly worse scores on a summary measure of cognition than the HIV+ CVD- group (NPZ8 score -0.57 vs 0.33, P = 0.04). CONCLUSIONS: This study demonstrates high rates of CVD in children with HIV despite antiretroviral therapy, and worse cognitive performance in children with CVD. Longitudinal studies are necessary to determine the mechanisms and incidence of new-onset CVD in children with HIV.
BACKGROUND:High rates of cerebrovascular disease (CVD) have previously been described in pediatric human immunodeficiency virus (HIV). However, little is known about pediatric CVD in the era of antiretroviral therapy or about the contribution of CVD to HIV-associated neurocognitive disorders. METHODS: We completed a neuroimaging substudy of the HIV-Associated Neurocognitive Disorders in Zambia study, a prospective cohort study of neurocognitive complications of pediatric HIV. Brain magnetic resonance imaging (1.5 T) was acquired for 34 HIV+ children on antiretroviral therapy and 17 HIV-exposed uninfected children (aged eight to 17 years). Demographics, medical history, neurological examination, and neuropsychologic testing results were collected. Two neuroradiologists, unaware of HIV status and clinical course, read the scans. RESULTS:CVD was identified in seven of 34 children with HIV (HIV+ CVD+) and no HIV-exposed uninfected children (21% vs 0%, P = 0.05). Three participants had white matter changes suggestive of small vessel disease, four had infarcts, and two had evidence of intracranial artery stenosis. Age of antiretroviral therapy initiation and exposure to protease inhibitors or efavirenz was not significantly different between children with and without CVD. HIV+ CVD+ children had significantly worse scores on a summary measure of cognition than the HIV+ CVD- group (NPZ8 score -0.57 vs 0.33, P = 0.04). CONCLUSIONS: This study demonstrates high rates of CVD in children with HIV despite antiretroviral therapy, and worse cognitive performance in children with CVD. Longitudinal studies are necessary to determine the mechanisms and incidence of new-onset CVD in children with HIV.
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