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.

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

Figure 1.

Multivariable-adjusted Cox proportional-hazards analysis of neurocognitive impairment as a function of anemia. This analysis included 799 CHARTER (CNS HIV Antiretroviral Therapy Effects Research) study participants who were neurocognitively normal at baseline and had longitudinal follow-up and data from 2545 visits. Global deficit scores (GDS) obtained after the baseline visit were adjusted for practice effects. Time-dependent, Cox proportional-hazards regression models were adjusted for age, sex, race/ethnicity, highly active antiretroviral therapy (on or off), nadir CD4⁺ T-cell count, zidovudine use, mean corpuscular volume at baseline, premorbid IQ (Wide-Range Achievement Test III score), and non–human immunodeficiency virus–related comorbid conditions at entry.