[HTML][HTML] Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

A Yilmaz, CT Yiannoutsos, D Fuchs, RW Price… - Journal of …, 2013 - Springer
A Yilmaz, CT Yiannoutsos, D Fuchs, RW Price, K Crozier, L Hagberg, S Spudich, M Gisslén
Journal of neuroinflammation, 2013Springer
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 …
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.
Springer