Blood Cell Indices and Neurocognitive Impairment in the HAART Era: a CHARTER Study.

Type: Poster
Title: Blood Cell Indices and Neurocognitive Impairment in the HAART Era: a CHARTER Study.
Authors: Kallianpur A, Wang Q, Jia P, McArthur JC, Morgello S, Collier AC, Gelman BB, Clifford DB, McCutchan JA, Grant I, and the CHARTER Study Group.
Year: 2014
Publication: Conference on Retroviruses and Opportunistic Infections

Background: Red blood count (RBC), mean cell volume (MCV), mean cell hemoglobin (MCH), and hemoglobin (Hgb) levels reflect both iron status and changes due to inflammation. Since iron is critical for maintenance of mitochondrial energetics and brain function, and anemia was a risk factor for HIV-associated dementia in the pre-HAART era, we examined the relationship of these indices to risk of neurocognitive disorders (HAND) in the HAART era.

Methods: We evaluated cross-sectional associations of red cell indices, and time-dependent associations of Hgb, with HAND in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study, a U.S.-based cohort study of neurological complications in the HAART era. CHARTER study subjects underwent standardized neurocognitive and neuromedical assessments, including RBC, MCV, MCH, and Hgb. HAND was defined by Frascati criteria (absence of neuromedical confounds, at least two impaired cognitive domains, and combined self-report and performance-based assessment of functional impairment). Adjusted β-coefficients (β), odds ratios (OR), or hazard ratios (HR) and their 95% confidence intervals (CIs) were estimated for RBC, MCV and MCH associations with HAND using multivariable (and for Hgb, also time-dependent) regression to adjust for age, sex, ethnicity, HAART, zidovudine (ZDV) use, CD4 nadir, plasma viral load, and wide-range achievement test score at entry.

Results: Neurocognitive performance data, red cell indices, and Hgb were available in 1235 CHARTER enrollees [median age 43 years, 23% women, med. CD4 nadir 181 cells/mm3, 864 (70%) on HAART, 17% ZDV use]. HAND was present in 584 subjects (43%) at entry. MCV and MCH were associated with HAND in unadjusted analyses [OR 1.02 (p=0.003) and OR 1.05 (p=0.005), respectively] and adjusted analyses [OR 1.02 for MCV (2% increase in risk per femtoliter rise in MCV, p=0.02 and OR 1.04 for MCH (4% increase in risk per picogram/cell rise in MCH, p=0.02, respectively]. MCV and MCH were also associated with cognitive impairment [Global Deficit Score (GDS)] as a continuous measure [β for MCV and MCH were 0.006 (p<0.001) and 0.015 (p<0.01), respectively]. RBC was inversely associated with continuous GDS (β= -0.054 (p=0.06), and anemia was associated with cognitive impairment (GDS≥0.5) over 18 to 36 months of follow-up (adjusted HR 1.21, p<0.01). Mild neurocognitive disorder was associated with RBC, MCV, and MCH [OR 0.57 (p=0.01), OR 1.03 (p=0.04), and OR 1.10 (p<0.01), respectively], and dementia was associated with MCV [OR 1.10 (p<0.05)].

Conclusions: Red cell indices and anemia, which as markers of iron metabolism are intimately linked to inflammation, oxygen delivery, and mitochondrial function, remain associated with HAND susceptibility in the HAART era.