title: Antiviral activity and CSF concentrations of 600/100 mg of darunavir/ritonavir once daily in HIV-1 patients with plasma viral suppression.
abstract: OBJECTIVE
  The objective of this study was to assess whether a lower dose than the currently used one of darunavir/ritonavir might achieve good CSF concentrations and contribute to inhibition of CNS viral replication.
  
  
  METHODS
  This was a substudy of a randomized, open, multicentre study (eudraCT 2011-006272-39), comparing the efficacy and safety of 800/100 mg of darunavir/ritonavir (darunavir 800) versus 600/100 mg of darunavir/ritonavir (darunavir 600) once daily plus tenofovir/emtricitabine or abacavir/lamivudine in 100 virologically suppressed patients. Paired blood and CSF samples were obtained. Total plasma darunavir concentrations were determined by HPLC, and CSF concentrations by liquid chromatography-tandem MS. Viral load (VL) was determined in plasma and CSF (limit of detection = 40 copies/mL) by PCR.
  
  
  RESULTS
  Sixteen patients were enrolled. The median (range) of darunavir CSF concentrations in darunavir 600 (n = 8) and darunavir 800 (n = 8) patients was 17.08 (5.79-30.19) and 13.23 (3.47-32.98) ng/mL, respectively (P = 0.916). The median (range) darunavir CSF:plasma ratio was 0.010 (0.005-0.022) in darunavir 600 patients and 0.008 (0.004-0.017) in the darunavir 800 arm (P = 0.370). All 16 patients had a VL < 40 copies/mL in plasma and 14 had a VL < 40 copies/mL in CSF. Of the two patients with detectable CSF VL (280 copies/mL and 159 copies/mL), one was receiving darunavir 600 and the other darunavir 800 plus tenofovir/emtricitabine. Of note, these patients had the lowest CSF darunavir concentrations in their respective groups: 5.79 ng/mL (802 ng/mL in plasma) and 3.47 ng/mL (958 ng/mL in plasma).
  
  
  CONCLUSIONS
  Darunavir CSF and plasma concentrations were comparable between the two arms. However, one patient from each group (with the lowest CSF darunavir concentrations in their respective groups) had detectable CSF VL despite undetectable plasma VL.
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Di Yacovo
authors.affiliation: Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrer
authors.affiliation: Hospital Vall d'Hebrón, Barcelona, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Curran
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Else
authors.affiliation: Department of Infectious Diseases, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
authors.affiliation: Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Fundació IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Universitat de Vic, Vic, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Tiraboschi
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Niubò
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vila
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.affiliation: Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain dpodzamczer@bellvitgehospital.cat.
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D000069454:Darunavir / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir; D000069454:Darunavir
keywords: ART; CSF; HIV/AIDS; antiretroviral therapy