Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era

J Infect Dis. 2016 Apr 1;213(7):1065-73. doi: 10.1093/infdis/jiv754. Epub 2015 Dec 21.

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.

Keywords: HIV-associated neurocognitive disorder; anemia; human immunodeficiency virus (HIV); iron metabolism; mitochondrial dysfunction; neurocognitive impairment; red blood cell indices.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Dementia Complex / etiology*
  • Adult
  • Anemia / blood
  • Anemia / complications*
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • Cohort Studies
  • Cross-Sectional Studies
  • Erythrocyte Count
  • Erythrocyte Indices*
  • Female
  • HIV Infections / blood
  • HIV Infections / complications*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Predictive Value of Tests
  • Risk Factors

Substances

  • Anti-HIV Agents