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Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy.

Journal article
Authors Aylin Yilmaz
Constantin T Yiannoutsos
Dietmar Fuchs
Richard W Price
Kathryn Crozier
Lars Hagberg
Serena Spudich
Magnus Gisslén
Published in Journal of neuroinflammation
Volume 10
Issue 1
Pages 62
ISSN 1742-2094
Publication year 2013
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 62
Language en
Links dx.doi.org/10.1186/1742-2094-10-62
https://gup.ub.gu.se/file/101087
Keywords HIV-1 RNA, Cerebrospinal fluid, Neopterin, Antiretroviral therapy
Subject categories Basic Medicine

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.

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