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. 2013 May 10:10:62.
doi: 10.1186/1742-2094-10-62.

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

Aylin Yilmaz  1 , Constantin T Yiannoutsos, Dietmar Fuchs, Richard W Price, Kathryn Crozier, Lars Hagberg, Serena Spudich, Magnus Gisslén
Affiliations

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

Aylin Yilmaz et al. J Neuroinflammation. .

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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Figures

Figure 1
Figure 1
Plot of observed data (circles), individual cerebrospinal fluid (CSF) neopterin decay curves (hashed grey lines) after initiation of antiretroviral therapy (at week 0) and average decay rate (solid orange curve).
Figure 2
Figure 2
Plot of observed data (circles), individual blood neopterin decay curves (hashed grey lines) after initiation of antiretroviral therapy (at week 0) and average decay rate (solid orange curve).
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