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Marked Increase of the Astrocytic Marker S100B in the Cerebrospinal Fluid of HIV-infected Patients on LPV/r-Monotherapy


Du Pasquier, Renaud A; Jilek, Samantha; Kalubi, Malela; Yerly, Sabine; Fux, Christoph A; Gutmann, Christine; Cusini, Alexia; Günthard, Huldrych F; Cavassini, Matthias; Vernazza, Pietro L (2013). Marked Increase of the Astrocytic Marker S100B in the Cerebrospinal Fluid of HIV-infected Patients on LPV/r-Monotherapy. AIDS (London, England), 27(2):203-210.

Abstract

OBJECTIVE: To determine changes of cerebrospinal fluid (CSF) biomarkers of subjects on monotherapy (MT) with lopinavir/ritonavir. DESIGN:: The MOST trial compared monotherapy with ritonavir-boosted lopinavir (MT) with continued therapy (CT). The trial was prematurely stopped due to virological failure in six patients on MT. It thus offers a unique opportunity to assess brain markers in the early stage of HIV virological escape. METHODS:: 65 CSF samples (34 on CT and 31 on MT) from 49 HIV+ patients enrolled in MOST. Using enzyme-linked immunosorbent assay, we determined the CSF concentration of S100B (astrocytosis), neopterin (inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-beta 1-42 (Abeta), the latter three indicating neuronal damage. Controls: CSF samples of 29 HIV-negative patients with Alzheimer dementia (AD). RESULTS:: In the CSF of MT, concentrations of S100B and neopterin were significantly higher than in CT (p = 0.006 and p = 0.013, respectively) and AD patients (p < 0.0001 and p = 0.0005, respectively). In AD, concentration of Abeta was lower than in MT (p = 0.005) and CT (p = 0.016) and concentrations of tTau were higher than in MT (p = 0.019) and CT (p = 0.001). There was no difference in pTau among the three groups. After removal of the 16 CSF with detectable viral load in the blood and/or CSF, only S100B remained significantly higher in MT than in the two other groups. CONCLUSIONS:: Despite full VL-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.

Abstract

OBJECTIVE: To determine changes of cerebrospinal fluid (CSF) biomarkers of subjects on monotherapy (MT) with lopinavir/ritonavir. DESIGN:: The MOST trial compared monotherapy with ritonavir-boosted lopinavir (MT) with continued therapy (CT). The trial was prematurely stopped due to virological failure in six patients on MT. It thus offers a unique opportunity to assess brain markers in the early stage of HIV virological escape. METHODS:: 65 CSF samples (34 on CT and 31 on MT) from 49 HIV+ patients enrolled in MOST. Using enzyme-linked immunosorbent assay, we determined the CSF concentration of S100B (astrocytosis), neopterin (inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-beta 1-42 (Abeta), the latter three indicating neuronal damage. Controls: CSF samples of 29 HIV-negative patients with Alzheimer dementia (AD). RESULTS:: In the CSF of MT, concentrations of S100B and neopterin were significantly higher than in CT (p = 0.006 and p = 0.013, respectively) and AD patients (p < 0.0001 and p = 0.0005, respectively). In AD, concentration of Abeta was lower than in MT (p = 0.005) and CT (p = 0.016) and concentrations of tTau were higher than in MT (p = 0.019) and CT (p = 0.001). There was no difference in pTau among the three groups. After removal of the 16 CSF with detectable viral load in the blood and/or CSF, only S100B remained significantly higher in MT than in the two other groups. CONCLUSIONS:: Despite full VL-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.

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10 citations in Web of Science®
13 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:13 Dec 2012 14:36
Last Modified:05 Apr 2016 16:11
Publisher:Lippincott, Williams & Wilkins
Series Name:AIDS
ISSN:0269-9370
Publisher DOI:https://doi.org/10.1097/QAD.0b013e32835a9a4a
PubMed ID:23032410

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