title: Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era.
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.
authors.affiliation: 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.
authors.forename: Asha R
authors.initials: AR
authors.lastname: Kallianpur
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Peilin
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Todd
authors.initials: T
authors.lastname: Hulgan
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.affiliation: Department of Neurosciences, University of California, San Diego.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: Department of Psychiatry, University of California, San Diego.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: Department of Neurology, University of Washington, Seattle.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.affiliation: Department of Neurology, Icahn School of Medicine of Mount Sinai, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Department of Neurology, Icahn School of Medicine of Mount Sinai, New York, New York.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: Department of Medicine, University of California, San Diego.
authors.forename: J A
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: Department of Psychiatry, University of California, San Diego.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D015526:AIDS Dementia Complex / Q000209:etiology*; D000328:Adult; D000740:Anemia / Q000097:blood / Q000150:complications*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004906:Erythrocyte Count; D004909:Erythrocyte Indices; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents
keywords: HIV-associated neurocognitive disorder; anemia; human immunodeficiency virus (HIV); iron metabolism; mitochondrial dysfunction; neurocognitive impairment; red blood cell indices