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


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.
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Arvid
A
Edén
Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
Thomas D
TD
Marcotte
Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
Robert K
RK
Heaton
Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
Staffan
S
Nilsson
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Institute of Neurology, University College London, London, United Kingdom.
Henrik
H
Zetterberg
Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
Dietmar
D
Fuchs
Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
Donald
D
Franklin
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
Richard W
RW
Price
Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
Igor
I
Grant
Department of Psychiatry, University of California San Diego, San Diego, California, United States of America.
Scott L
SL
Letendre
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Magnus
M
Gisslén
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000276:immunology; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid* / Q000276:immunology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid* / Q000276:immunology
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D019798:Neopterin