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

• Published in: PloS one Vol. 11; no. 6; p. e0157160
• Main Authors: Edén, Arvid, Marcotte, Thomas D., Heaton, Robert K., Nilsson, Staffan, Zetterberg, Henrik, Fuchs, Dietmar, Franklin, Donald, Price, Richard W., Grant, Igor, Letendre, Scott L., Gisslén, Magnus
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.06.2016; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Activation; Adult; AIDS; AIDS Dementia Complex - cerebrospinal fluid; AIDS Dementia Complex - drug therapy; AIDS Dementia Complex - immunology; Analysis; Anti-Retroviral Agents - therapeutic use; antiretroviral; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biology and Life Sciences; Biomarkers; Biomarkers - cerebrospinal fluid; Brain research; Care and treatment; Central nervous system; Cerebrospinal fluid; cerebrospinal-fluid neopterin; Cognition; Cognitive ability; Correlation; csf; deficit scores; Dementia; disorders; Dosage and administration; Drug therapy; Drug use; Female; Health aspects; Highly active antiretroviral therapy; HIV; HIV-1 - drug effects; HIV-1 - immunology; hiv-1 infection; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune response; Impairment; Infections; Infectious diseases; Infectious Medicine; Infektionsmedicin; Lentivirus; Longitudinal Studies; Male; Medicine and Health Sciences; Middle Aged; Neopterin; Neopterin - cerebrospinal fluid; Neopterin - immunology; neurofilament protein; Neurofilament Proteins - cerebrospinal fluid; Neurofilament Proteins - immunology; Neurology; Neuropsychology; Patients; prevalence; Psychiatry; Retroviridae; Social Sciences; Studies; Therapy; United States; San Francisco California; Sweden; California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157160

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.