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

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 neu...

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Published inPloS 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.
OBJECTIVEAlthough 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 METHODSWe 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.RESULTSGeometric 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).CONCLUSIONSMild 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.
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.
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.
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.
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
Audience Academic
Author Nilsson, Staffan
Marcotte, Thomas D.
Price, Richard W.
Letendre, Scott L.
Gisslén, Magnus
Heaton, Robert K.
Fuchs, Dietmar
Zetterberg, Henrik
Franklin, Donald
Edén, Arvid
Grant, Igor
AuthorAffiliation 4 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
5 Institute of Neurology, University College London, London, United Kingdom
7 Department of Neurology, University of California San Francisco, San Francisco, California, United States of America
1 Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
UNSW Australia, AUSTRALIA
2 Department of Psychiatry, University of California San Diego, San Diego, California, United States of America
3 Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
6 Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
AuthorAffiliation_xml – name: 7 Department of Neurology, University of California San Francisco, San Francisco, California, United States of America
– name: 1 Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
– name: 2 Department of Psychiatry, University of California San Diego, San Diego, California, United States of America
– name: 3 Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden
– name: 6 Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
– name: 5 Institute of Neurology, University College London, London, United Kingdom
– name: UNSW Australia, AUSTRALIA
– name: 4 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Author_xml – sequence: 1
  givenname: Arvid
  surname: Edén
  fullname: Edén, Arvid
– sequence: 2
  givenname: Thomas D.
  surname: Marcotte
  fullname: Marcotte, Thomas D.
– sequence: 3
  givenname: Robert K.
  surname: Heaton
  fullname: Heaton, Robert K.
– sequence: 4
  givenname: Staffan
  surname: Nilsson
  fullname: Nilsson, Staffan
– sequence: 5
  givenname: Henrik
  surname: Zetterberg
  fullname: Zetterberg, Henrik
– sequence: 6
  givenname: Dietmar
  surname: Fuchs
  fullname: Fuchs, Dietmar
– sequence: 7
  givenname: Donald
  surname: Franklin
  fullname: Franklin, Donald
– sequence: 8
  givenname: Richard W.
  surname: Price
  fullname: Price, Richard W.
– sequence: 9
  givenname: Igor
  surname: Grant
  fullname: Grant, Igor
– sequence: 10
  givenname: Scott L.
  surname: Letendre
  fullname: Letendre, Scott L.
– sequence: 11
  givenname: Magnus
  surname: Gisslén
  fullname: Gisslén, Magnus
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27295036$$D View this record in MEDLINE/PubMed
https://gup.ub.gu.se/publication/240034$$DView record from Swedish Publication Index
https://research.chalmers.se/publication/240034$$DView record from Swedish Publication Index
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ContentType Journal Article
Copyright COPYRIGHT 2016 Public Library of Science
2016 Edén et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2016 Edén et al 2016 Edén et al
Copyright_xml – notice: COPYRIGHT 2016 Public Library of Science
– notice: 2016 Edén et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2016 Edén et al 2016 Edén et al
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Virology and AIDS Abstracts
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Competing Interests: The authors have read the journal's policy and have the following competing interests. AE reports receiving travel grants from Gilead and BMS, and lecture honoraria from AbbVie. MG reports receiving honoraria as speaker and/or advisor from AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, and Merck. HZ is co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Holding-based platform company at the University of Gothenburg. Funds to support research projects have been paid to UC San Diego on behalf of SLL by Abbvie, Gilead Sciences, Merck & Co., and ViiV Healthcare. Honoraria have also been paid to SLL for educational lectures (Abbvie, Janssen) or advisory boards (Cipla, Janssen, Merck & Co., and ViiV Healthcare). RWP reports receiving honoraria as speaker and/or advisor from Gilead, Merck. All other authors declare no conflict of interest. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: MG RWP. Performed the experiments: D. Fuchs HZ. Analyzed the data: AE MG SN. Wrote the paper: AE TDM RKH SN HZ D. Fuchs D. Franklin RWP IG SLL MG. Designed, performed, and coordinated the parent study (CHARTER) as well as the substudy (the NIMH AIDS Research Center (ARC) Biomarker project): IG RKH SLL TDM D. Franklin. Reviewed and identified the cases for the project: SLL TDM D. Franklin.
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SSID ssj0053866
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Snippet Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients...
Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in...
OBJECTIVEAlthough milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in...
ObjectiveAlthough milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in...
Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in...
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SubjectTerms 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
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Title Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment
URI https://www.ncbi.nlm.nih.gov/pubmed/27295036
https://www.proquest.com/docview/1796245397
https://www.proquest.com/docview/1797253530
https://www.proquest.com/docview/1808685231
https://pubmed.ncbi.nlm.nih.gov/PMC4905676
https://gup.ub.gu.se/publication/240034
https://research.chalmers.se/publication/240034
https://doaj.org/article/76e001bde3664fa9963c57abd598f660
http://dx.doi.org/10.1371/journal.pone.0157160
Volume 11
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