Asha R Kallianpur1, Quan Wang2, Peilin Jia2, Todd Hulgan3, Zhongming Zhao2, Scott L Letendre4, Ronald J Ellis5, Robert K Heaton6, Donald R Franklin4, Jill Barnholtz-Sloan7, Ann C Collier8, Christina M Marra9, David B Clifford10, Benjamin B Gelman11, Justin C McArthur12, Susan Morgello13, David M Simpson13, J A McCutchan4, Igor Grant6. 1. Department of Genomic Medicine/Lerner Research Institute and Medicine Institute, Cleveland Clinic Foundation, Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. 2. Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee. 3. Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. 4. Department of Medicine, University of California, San Diego. 5. Department of Neurosciences, University of California, San Diego. 6. Department of Psychiatry, University of California, San Diego. 7. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. 8. Department of Medicine, University of Washington, Seattle. 9. Department of Neurology, University of Washington, Seattle. 10. Department of Neurology, Washington University School of Medicine, St Louis, Missouri. 11. Department of Pathology, University of Texas Medical Branch, Galveston, Johns Hopkins University School of Medicine, Baltimore, Maryland. 12. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 13. Department of Neurology, Icahn School of Medicine of Mount Sinai, New York, New York.
Abstract
BACKGROUND: Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. METHODS: We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. RESULTS: HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). CONCLUSIONS: Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.
BACKGROUND:Anemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infectedpersons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown. METHODS: We evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments. RESULTS: HAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01). CONCLUSIONS:Anemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infectedpersons.
Keywords:
HIV-associated neurocognitive disorder; anemia; human immunodeficiency virus (HIV); iron metabolism; mitochondrial dysfunction; neurocognitive impairment; red blood cell indices
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