Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

Aylin Yilmaz, Constantin Yiannoutsos, Dietmar Fuchs, Richard W. Price, Kathryn Crozier, Lars Hagberg, Serena Spudich, Magnus Gisslén

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression.Methods: CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison.Results: Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels.Conclusions: After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.

Original languageEnglish
Article number62
JournalJournal of Neuroinflammation
Volume10
DOIs
StatePublished - May 10 2013

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Neopterin
Cerebrospinal Fluid
AIDS Dementia Complex
Dementia
Therapeutics
Macrophage Activation
HIV
Nonlinear Dynamics

Keywords

  • Antiretroviral therapy
  • Cerebrospinal fluid
  • HIV-1 RNA
  • Neopterin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology
  • Neuroscience(all)

Cite this

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. / Yilmaz, Aylin; Yiannoutsos, Constantin; Fuchs, Dietmar; Price, Richard W.; Crozier, Kathryn; Hagberg, Lars; Spudich, Serena; Gisslén, Magnus.

In: Journal of Neuroinflammation, Vol. 10, 62, 10.05.2013.

Research output: Contribution to journalArticle

Yilmaz, Aylin ; Yiannoutsos, Constantin ; Fuchs, Dietmar ; Price, Richard W. ; Crozier, Kathryn ; Hagberg, Lars ; Spudich, Serena ; Gisslén, Magnus. / Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy. In: Journal of Neuroinflammation. 2013 ; Vol. 10.
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abstract = "Background: Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression.Methods: CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-na{\"i}ve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison.Results: Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59{\%}) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14{\%} of HAD patients were predicted to reach normal levels.Conclusions: After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41{\%} of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.",
keywords = "Antiretroviral therapy, Cerebrospinal fluid, HIV-1 RNA, Neopterin",
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AU - Yilmaz, Aylin

AU - Yiannoutsos, Constantin

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AU - Crozier, Kathryn

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N2 - Background: Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression.Methods: CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison.Results: Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels.Conclusions: After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.

AB - Background: Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression.Methods: CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison.Results: Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels.Conclusions: After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation.

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