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

TitleIncreased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment.
Publication TypeJournal Article
Year of Publication2016
AuthorsEdén, A, Marcotte, TD, Heaton, RK, Nilsson, S, Zetterberg, H, Fuchs, D, Franklin, D, Price, RW, Grant, I, Letendre, S, Gisslén, M
JournalPLoS One
Date Published2016
KeywordsAdult, AIDS Dementia Complex, Anti-Retroviral Agents, Biomarkers, CHARTER, External, Female, HIV-1, Humans, Longitudinal Studies, Male, Middle Aged, Neopterin, Neurofilament Proteins

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).DESIGN AND METHODS: 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.RESULTS: 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).CONCLUSIONS: 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.

Alternate JournalPLoS ONE
PubMed ID27295036
PubMed Central IDPMC4905676
Grant ListK24 MH097673 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States
R01 NS094067 / NS / NINDS NIH HHS / United States