title: Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy.
  
  
  METHODS
  This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible.We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate.
  
  
  RESULTS
  HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms.
  
  
  CONCLUSIONS
  CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.
authors.affiliation: Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute Neuroradiology Unit, Head and Neck Department, IRCCS San Raffaele Scientific Institute, Milan, Italy Department of Infectious Diseases, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK Division of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferretti
authors.forename: Alba
authors.initials: A
authors.lastname: Bigoloni
authors.forename: Laura
authors.initials: L
authors.lastname: Passeri
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Valeria
authors.initials: V
authors.lastname: Longo
authors.forename: Simonetta
authors.initials: S
authors.lastname: Gerevini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Spagnuolo
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslen
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Giada
authors.initials: G
authors.lastname: Caramatti
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood* / Q000134:cerebrospinal fluid*; D064420:Drug-Related Side Effects and Adverse Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction; D019438:Ritonavir / Q000627:therapeutic use*; D013129:Spinal Puncture; D019562:Viral Load / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D017320:HIV Protease Inhibitors; D000069446:Atazanavir Sulfate; D019438:Ritonavir