title: Rilpivirine exposure in plasma and sanctuary site compartments after switching from nevirapine-containing combined antiretroviral therapy.
abstract: OBJECTIVE
  Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine.
  
  
  METHODS
  HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively).
  
  
  RESULTS
  Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90.
  
  
  CONCLUSIONS
  Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP.
authors: Faculty of Medicine, Imperial College, London, UK Department of HIV and Genitourinary Medicine, Imperial College Healthcare NHS Trust St Mary's Hospital, London, UK b.mora-peris@imperial.ac.uk.
authors: Borja
authors: B
authors: Mora-Peris
authors: Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, UK.
authors: Victoria
authors: V
authors: Watson
authors: Faculty of Medicine, Imperial College, London, UK Department of HIV and Genitourinary Medicine, Imperial College Healthcare NHS Trust St Mary's Hospital, London, UK.
authors: Jaime H
authors: JH
authors: Vera
authors: Department of HIV and Genitourinary Medicine, Imperial College Healthcare NHS Trust St Mary's Hospital, London, UK.
authors: Rosy
authors: R
authors: Weston
authors: Faculty of Medicine, Imperial College, London, UK.
authors: Adam D
authors: AD
authors: Waldman
authors: Faculty of Medicine, Imperial College, London, UK.
authors: Steve
authors: S
authors: Kaye
authors: Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, UK.
authors: Saye
authors: S
authors: Khoo
authors: Faculty of Medicine, Imperial College, London, UK Department of HIV and Genitourinary Medicine, Imperial College Healthcare NHS Trust St Mary's Hospital, London, UK.
authors: Nicola E
authors: NE
authors: Mackie
authors: Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, UK.
authors: David
authors: D
authors: Back
authors: Faculty of Medicine, Imperial College, London, UK Department of HIV and Genitourinary Medicine, Imperial College Healthcare NHS Trust St Mary's Hospital, London, UK.
authors: Alan
authors: A
authors: Winston
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002555:Cerebrospinal Fluid / Q000378:metabolism; D057915:Drug Substitution; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068696:Rilpivirine; D012661:Semen / Q000378:metabolism; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D019829:Nevirapine; D000068696:Rilpivirine
keywords: CSF; nevirapine; seminal plasma; switch