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Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

Journal article
Authors Arvid Edén
T. D. Marcotte
R. K. Heaton
Staffan Nilsson
Henrik Zetterberg
D. Fuchs
D. Franklin
R. W. Price
I. Grant
S. L. Letendre
Magnus Gisslén
Published in Plos One
Volume 11
Issue 6
Pages 0157160
ISSN 1932-6203
Publication year 2016
Published at Department of Mathematical Sciences, Mathematical Statistics
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Biomedicine, Department of Infectious Medicine
Pages 0157160
Language en
Links dx.doi.org/10.1371/journal.pone.015...
https://gup.ub.gu.se/file/198089
Keywords cerebrospinal-fluid neopterin, central-nervous-system, antiretroviral, therapy, neurofilament protein, hiv-1 infection, deficit scores, disorders, csf, prevalence, biomarkers
Subject categories Infectious Medicine

Abstract

Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies.

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