title: Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.
abstract: OBJECTIVE
  To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum.
  
  
  METHODS
  This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929.
  
  
  RESULTS
  Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was <300 copies/mL in all but two patients. All children were tested HIV-negative and no congenital abnormalities were reported.
  
  
  CONCLUSIONS
  Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy.
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands angela.colbers@radboudumc.nl.
authors.forename: Angela
authors.initials: A
authors.lastname: Colbers
authors.affiliation: Hospital Universitari Germans Trias I Pujol, Badalona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.affiliation: National Institute for Infectious Diseases 'L. Spallanzani', Rome, Italy.
authors.forename: Jelena
authors.initials: J
authors.lastname: Ivanovic
authors.affiliation: Saint-Pierre University Hospital, Brussels, Belgium.
authors.forename: Kabamba
authors.initials: K
authors.lastname: Kabeya
authors.affiliation: Chelsea & Westminster Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hawkins
authors.affiliation: Klinikum der Universität München, Frauenklinik Innenstadt, München, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gingelmaier
authors.affiliation: Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Taylor
authors.affiliation: Klinik für Geburtsmedizin, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weizsäcker
authors.affiliation: Institution for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: S Tariq
authors.initials: ST
authors.lastname: Sadiq
authors.affiliation: Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marchina
authors.initials: M
authors.lastname: Van der Ende
authors.affiliation: University of Padua, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: Burger
mesh_terms: D000328:Adult; D000069454:Darunavir; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D000069454:Darunavir
keywords: HIV; antiretroviral; pharmacokinetics; protease inhibitors; transplacental passage