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, 27(2), pp. 203-210. Lippincott Williams & Wilkins 10.1097/QAD.0b013e32835a9a4a

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Objective: To determine changes of cerebrospinal fluid (CSF) biomarkers of patients on monotherapy with lopinavir/ritonavir. Design: The Monotherapy Switzerland/Thailand study (MOST) trial compared monotherapy with ritonavir-boosted lopinavir with continued therapy. The trial was prematurely stopped due to virological failure in six patients on monotherapy. It, thus, offers a unique opportunity to assess brain markers in the early stage of HIV virological escape. Methods: Sixty-five CSF samples (34 on continued therapy and 31 on monotherapy) from 49 HIV-positive 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-β 1–42 (Aβ), the latter three indicating neuronal damage. Controls were CSF samples of 29 HIV-negative patients with Alzheimer dementia. Results: In the CSF of monotherapy, concentrations of S100B and neopterin were significantly higher than in continued therapy (P = 0.006 and P = 0.013, respectively) and Alzheimer dementia patients (P < 0.0001 and P = 0.0005, respectively). In Alzheimer dementia, concentration of Aβ was lower than in monotherapy (P = 0.005) and continued therapy (P = 0.016) and concentrations of tTau were higher than in monotherapy (P = 0.019) and continued therapy (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 monotherapy than in the two other groups. Conclusion: Despite full viral load-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Fux, Christoph Andreas and Cusini, Alexia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0269-9370

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

21 Mar 2014 11:15

Last Modified:

19 Oct 2015 11:17

Publisher DOI:

10.1097/QAD.0b013e32835a9a4a

Uncontrolled Keywords:

astrocyte, central nervous system, HIV, lopinavir-ritonavir, monotherapy, neopterin, S100B

BORIS DOI:

10.7892/boris.44635

URI:

https://boris.unibe.ch/id/eprint/44635

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