Open Access Research

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

Aylin Yilmaz1*, Constantin T Yiannoutsos2, Dietmar Fuchs3, Richard W Price4, Kathryn Crozier4, Lars Hagberg1, Serena Spudich5 and Magnus Gisslén1

Author Affiliations

1 Department of Infectious Diseases, University of Gothenburg, Journalvagen 10, Gothenburg, 416 50, Sweden

2 Department of Biostatistics, Indiana University R.M. Fairbanks School of Public Health, 410 West 10th Street, Indianapolis, IN, 46202, USA

3 Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Center for Chemistry and Biomedicine, Innrain 80, 4th Floor, Innsbruck, A-6020, Austria

4 Department of Neurology, University of California San Francisco, San Francisco Genreal Hospital, 1001 Potrero Avenue, San Francisco, California, 94110, USA

5 Department of Neurology, Yale University School of Medicine, 300 George Street, New Haven, Connecticut, 06510, USA

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Journal of Neuroinflammation 2013, 10:62  doi:10.1186/1742-2094-10-62

Published: 10 May 2013

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.

Keywords:
HIV-1 RNA; Cerebrospinal fluid; Neopterin; Antiretroviral therapy