title: Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.
abstract: BACKGROUND
  The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.
  
  
  METHODS
  An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated.
  
  
  RESULTS
  Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9).
  
  
  CONCLUSIONS
  Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women.
  
  
  BACKGROUND
  NCT00825929.
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Maren I
authors.initials: MI
authors.lastname: Blonk
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Angela P H
authors.initials: AP
authors.lastname: Colbers
authors.affiliation: Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Hidalgo-Tenorio
authors.affiliation: Saint-Pierre University Hospital, Brussels, Belgium.
authors.forename: Kabamba
authors.initials: K
authors.lastname: Kabeya
authors.affiliation: Klinik für Geburtsmedizin, Charité Universitätsmedizin, Berlin.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weizsäcker
authors.affiliation: Universitätsklinikum Frankfurt, Medizinische Klinik II, Germany.
authors.forename: Annette E
authors.initials: AE
authors.lastname: Haberl
authors.affiliation: Hospital Universitari Germans Trias i Pujol, 'Lluita contra la Sida' Foundation, Badalona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.affiliation: Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Hawkins
authors.affiliation: Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marchina E
authors.initials: ME
authors.lastname: van der Ende
authors.affiliation: Klinikum der Universität München, Frauenklinik Innenstadt, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gingelmaier
authors.affiliation: Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.affiliation: National Institute for Infectious Diseases 'L. Spallanzani,' Rome.
authors.forename: Jelena
authors.initials: J
authors.lastname: Ivanovic
authors.affiliation: University of Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000453:epidemiology; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000068898:Raltegravir Potassium
keywords: HIV; MTCT; pharmacokinetics; pregnancy; raltegravir