Anemia and red blood cell indices predict HIV-associated neurocognitive impairment in the highly active antiretroviral therapy era

Asha R. Kallianpur, Quan Wang, Peilin Jia, Todd Hulgan, Zhongming Zhao, Scott L. Letendre, Ronald J. Ellis, Robert K. Heaton, Donald R. Franklin, Jill Barnholtz-Sloan, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin B. Gelman, Justin C. McArthur, Susan Morgello, David M. Simpson, J. A. McCutchan, Igor Grant, J. Allen McCutchanThomas D. Marcotte, Donald Franklin, Terry Alexander, Edmund Capparelli, J. Hampton Atkinson, Steven Paul Woods, Matthew Dawson, David M. Smith, Christine Fennema-Notestine, Michael J. Taylor, Rebecca Theilmann, Anthony C. Gamst, Clint Cushman, Ian Abramson, Florin Vaida, Jennifer Marquie-Beck, Vincent Rogalski, David Simpson, Letty Mintz, Will Toperoff, Ann Collier, Christina Marra, Trudy Jones, Benjamin Gelman, Eleanor Head, Muhammad Al-Lozi, Mengesha Teshome

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish
Pages (from-to)1065-1073
Number of pages9
JournalJournal of Infectious Diseases
Issue number7
StatePublished - Apr 1 2016


  • Anemia
  • HIV-associated neurocognitive disorder
  • Human immunodeficiency virus (HIV)
  • Iron metabolism
  • Mitochondrial dysfunction
  • Neurocognitive impairment
  • Red blood cell indices


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