Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients

• Published in: PloS one Vol. 9; no. 2; p. e88591
• Main Authors: Jessen Krut, Jan, Mellberg, Tomas, Price, Richard W, Hagberg, Lars, Fuchs, Dietmar, Rosengren, Lars, Nilsson, Staffan, Zetterberg, Henrik, Gisslén, Magnus
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.02.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; Aging; AIDS; AIDS Dementia Complex - cerebrospinal fluid; Albumin; Albumins; Antiretroviral agents; Antiretroviral drugs; Axons - pathology; Biology; Biomarkers; Biomarkers - metabolism; blood counts; Blood-brain barrier; brain damage; Brain injuries; Brain injury; Case-Control Studies; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; Central nervous system; Cerebrospinal fluid; Clinical Medicine; Cognition; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - complications; Correlation; Cross-Sectional Studies; Dementia disorders; Head injuries; Health aspects; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - cerebrospinal fluid; HIV Infections - complications; HIV patients; HIV-1; Human immunodeficiency virus; Humans; Inflammation; Klinisk medicin; Longitudinal Studies; Medicine; Membrane permeability; Middle Aged; Neopterin; Neopterin - cerebrospinal fluid; Neurodegeneration; Neurofilament Proteins - cerebrospinal fluid; Neurofilaments; Neurons - metabolism; Neuropsychological testing; Neurosciences; Neurovetenskaper; Patients; Permeability; Studies; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088591

Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.