Publication Abstract Display
Type: Published Abstract
Title: CNS immunoactivation and neuronal damage in patients with progressive neurocognitive impairment.
Authors:
Year: 2015
Publication: 2015 Annual Conference on Retroviruses and Opportunistic Infections
Volume: Issue: Pages:
Abstract:Background Although HIV-associated neurocognitive disorders (HAND) remain prevalent, the clinical significance is unclear. A recent report indicates a higher risk of symptomatic progression in subjects with asymptomatic neurocognitive impairment (ANI) than in unimpaired subjects. In a previous cross sectional analysis, we found that subjects with neurocognitive impairment (NCI) had increased cerebrospinal fluid (CSF) levels of neopterin but not neurofilament protein light subunit (NFL) compared to unimpaired subjects. Here, we investigated if a decline in neurocognitive performance (NP) was associated with ongoing neuronal damage measured by CSF NFL in a well characterized cohort of virally suppressed subjects. Methods Subjects on antiretroviral therapy (ART) with plasma HIV-1 RNA <50 c/ml without significant confounding conditions were identified from longitudinal studies (CHARTER and HNRC). Standardized NP testing was performed on two separate occasions. Subjects were classified as NP normal (NPN) or NCI (including subjects with ANI or mild neurocognitive disorder (MND)). According to NP test stability, subjects were categorized as NP stable or NP decline. CSF NFL was measured by enzymatic 2-site quantitative immunoassay (UmanDiagnostics, Umea, Sweden). CSF neopterin was measured by ELISA. The difference in CSF biomarkers between NCI and NPN were analyzed using a mixed effects model adjusting for age. Mann Whitney test was used to explore change in biomarkers according to NP progress. Correlations were explored using Pearson correlation. Results 100 (91% male) subjects were included in the analysis, 29 NPN and 71 with NCI (ANI=38; MND=33). 32 subjects (all in the NCI-group) had a NP decline from baseline to follow up. We found no differences in change of CSF NFL or neopterin in subjects with NP decline compared to NP stable subjects. However, the NCI-group had 17 % higher age-adjusted NFL (P=0.08) and 27 % higher neopterin (P=0.03) compared to the NPN-group. Neopterin was significantly correlated with NFL in the NCI-group (r=0.38; P=0.001), but not in the NPN-group (R=-0.17; P=0.4). Conclusions We did not find any difference in CSF NFL or neopterin in virologically suppressed subjects with progressive neurocognitive impairment compared to subjects without functional decline. However, the correlation found between CSF neopterin and NFL in subjects with NCI indicates an association between immune activation, neuronal damage and neurocognitive impairment that needs to be further characterized.

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