title: Marked increase of the astrocytic marker S100B in the cerebrospinal fluid of HIV-infected patients on LPV/r-monotherapy.
abstract: OBJECTIVE
  To determine changes of cerebrospinal fluid (CSF) biomarkers of patients on monotherapy with lopinavir/ritonavir.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Despite full viral load-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.
authors.affiliation: Unit of Neuroimmunology, Division of Neurology and Division of Immunology, Department of Clinical Neurosciences and Department of Medicine, University Hospital of Lausanne, University of Lausanne, Lausanne 1011, Switzerland. Renaud.du-pasquier@chuv.ch
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
authors.forename: Samantha
authors.initials: S
authors.lastname: Jilek
authors.forename: Malela
authors.initials: M
authors.lastname: Kalubi
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.forename: Christine
authors.initials: C
authors.lastname: Gutmann
authors.forename: Alexia
authors.initials: A
authors.lastname: Cusini
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Vernazza
mesh_terms: D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000187:drug effects; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001253:Astrocytes / Q000187:drug effects; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use*; D019798:Neopterin / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000187:drug effects; D019438:Ritonavir / Q000627:therapeutic use*; D009418:S100 Proteins / Q000134:cerebrospinal fluid*; D013557:Switzerland; D013785:Thailand; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D017320:HIV Protease Inhibitors; D010446:Peptide Fragments; D009418:S100 Proteins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D061466:Lopinavir; D019798:Neopterin; D019438:Ritonavir