8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:44 (abstract no. 7)

Ryan LA, Zheng J, Brester M, Bohac D, Hahn F, Gendelman HE, Swindells S;
Univ of Nebraska Med Ctr, Omaha.

BACKGROUND: The role of peripheral immune responses in the pathogenesis of HIV-1 associated dementia (HAD) was investigated through a prospective study of 28 patients with advanced HIV-1 disease with or without neurological dysfunction. All patients were on potent antiretroviral therapy.

METHODS: Clinical, immune, viral, neuropsychological, and neuroradiological tests were performed at three month intervals for two years. At enrollment, the mean numbers of CD4+ T lymphocytes and viral load were 197.8 cells/mm³ and 87,886 copies/ml respectively. Patients were stratified as neuropsychologically normal (n = 8, NPZ = 0) or impaired (n = 20, NPZ ≤ 0.5) and by the presence (n = 11) or absence (n = 17) of brain atrophy on magnetic resonance imaging (MRI). Peripheral immune activity was determined by measuring levels of soluble tumor necrosis factor-alpha receptor two (sTNF-R2) and soluble CD14 (sCD14) in patient plasma by ELISA. These parameters were correlated with neuropsychological (NPZ), MRI and magnetic resonance spectroscopy (MRS) findings and analyzed by Spearman rank correlation coefficient testing. MRS measurements included N-acetyl aspartate (NAA): creatinine (CR) ratios, which indicate neuronal loss, and myoinositol (MI): CR and choline (CHO): CR ratios, which suggest gliosis.

RESULTS: Preliminary results demonstrate that patients with brain atrophy have significantly higher MI: CR and CHO: CR ratios (p<0.05). There was no significant difference in either ratio when the patients were grouped by NPZ score. Both sCD14 and sTNF-R2 correlated significantly (p<0.05) with MI: CR (R = 0.29 and R = 0.51) and CHO: CR (R = 0.4 and R = 0.59) measurements, but only sTNF-R2 demonstrated a significant correlation to NAA: CR (R = 0.36). Both sCD14 and sTNF-R2 exhibited significantly (p<0.01) higher levels in patients with brain atrophy (2041 + 197.3 pg/ml and 3.84 + 0.38 ng/ml respectively) when compared to those with normal MRIs (1456 + 94.12 pg/ml and 2.48 + 0.29 ng/ml). sCD14 levels were also significantly correlated with NPZ scores (R=0.31, p<0.05).

CONCLUSIONS: These findings not only demonstrate a role for peripheral immune activation in HAD pathogenesis but also suggest that plasma levels of sTNF-R2 and sCD14 can be used with MRI and MRS techniques to monitor neurological dysfunction during progressive HIV-1 disease.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.