Publication Abstract Display | Type: Published Abstract | Title: Lithium improves HIV-associated neurocognitive impairment. | Authors: Letendre S, Woods S, Ellis R, Atkinson J, van den Brande G, Durelle J, Grant I, and the HNRC Group | Year: 2004 | Publication: 11th Annual Conference on Retroviruses and Opportunistic Infections | Volume: Session 74 Issue: Pages: 492 | Abstract:Background: Lithium may protect neurons by several mechanisms, including modulation of Na+/K+ ion channels and 2) proteins associated with
inflammation and apoptosis. The primary objective of this pilot study was to identify the effects of low-dose lithium on the NP performance of HIV-infected
subjects with baseline neuropsychological (NP) impairment.
Methods: The study was a single-arm, open-label, pilot study of 12 weeks of low-dose oral lithium in HIV-infected subjects who had globally impaired
performance on a standardized, battery of NP tests at entry. Lithium was initiated at 300 mg daily and was titrated to maintain 12-hour trough concentrations
between 0.4 and 0.8 mEq/L. Study assessments included NP testing, neuromedical exams, phlebotomy, and lumbar puncture. All subjects were on stable
antiretroviral therapy. HIV RNA was measured by RT-PCR, CD4 counts by flow cytometry, and immune markers by ELISA. NP test results were
summarized using the global deficit score (GDS), a validated measure that accounts for performance in 7 cognitive domains and adjusts for age, education,
and ethnicity. Baseline and week 12 values of continuous variables were compared with one-way paired t-tests.
Results: We screened 21 subjects and enrolled 8. Enrolled subjects were mostly middle-aged (median 44 years), well educated (median 14 years), caucasian
(50%) men (88%). At baseline, the median CD4 count was 292/μL and 7 subjects had HIV RNA levels in plasma < 400 c/mL. Titrated lithium doses ranged
between 600 and 1200 mg per day. NP performance improved in all 8 subjects after 12 weeks of lithium therapy (median GDS 0.74 (baseline) vs. 0.44 (12
weeks), p = 0.02). Median deficit reduction was 0.29. HIV RNA levels in plasma and CSF remained stable between baseline and week 12 (both p>.10) but
CD4 counts may have declined (median change -93/μL, p = 0.10). Concentrations of soluble tumor necrosis factor receptors (sTNFR)-II seemed to increase in
plasma (mean 2900 vs 3193 pg/mL, p = 0.09). The study treatment was well tolerated overall with no grade 3 or 4 adverse events and no premature
discontinuations.
Conclusions: Treatment with low doses of lithium was associated with improvements in NP performance in this small, uncontrolled study. Lithium may
improve performance by increasing expression of soluble TNF receptors, which can bind the neurotoxin, TNF-a. The study drug was well tolerated but may
have reduced CD4 counts. |
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