title: Pharmacokinetics, safety and efficacy of ritonavir-boosted atazanavir (300/100 mg once daily) in HIV-1-infected pregnant women.
abstract: BACKGROUND
  Atazanavir/ritonavir (ATV/r) is a boosted protease inhibitor recommended to minimize the risk of mother-to-child HIV-1 transmission (MTCT). We aimed to assess the pharmacokinetics, safety and efficacy of ATV/r in HIV-1-infected pregnant women and their neonates.
  
  
  METHODS
  A multicentre, cross-sectional, non-interventional cohort of HIV-1-infected pregnant women receiving ATV/r (300/100 mg once daily) who delivered in three Paris hospitals from 2006 to 2013 was designed. We determined antiretroviral trough plasma concentrations using liquid chromatography-mass spectrometry at each of the three trimesters, delivery and post-partum. ATV concentrations at 24 h (C24h) were interpreted by the 150-850 ng/ml efficacy-tolerance thresholds. Safety data and newborn HIV status were recorded. A mother's virological failure was defined as two successive measurements of plasma HIV-1 RNA>50 copies/ml within the 2 months before delivery.
  
  
  RESULTS
  103 pregnant women were included, mostly from sub-Saharan Africa (88%). ATV C24h at each of the three trimesters and delivery remained similar to post-partum values. No dose adjustment was needed during pregnancy. The median plasma ratio of fetal/maternal ATV level was 0.19 (n=28). Only three patients showed two successive detectable viral loads but <400 copies/ml. Among 82 available newborn data, 16 were born preterm. Three in utero deaths occurred. Tolerance was good with one case of maternal grade 3 hyperbilirubinaemia, no cases in neonates at delivery and no clinically relevant adverse event. No case of MTCT was reported.
  
  
  CONCLUSIONS
  In this population, an ATV/r-containing antiretroviral regimen demonstrated good pharmacokinetics, virological efficacy and safety. No significant impact of pregnancy on ATV C24h was found. No dose adjustment was required.
authors.affiliation: APHP, Bichat-Claude Bernard Hospital, Clinical Pharmaco-Toxicology Department, Hôpitaux Universitaires Paris Nord Val de Seine, Paris, France. minh.le@bch.aphp.fr.
authors.forename: Minh P
authors.initials: MP
authors.lastname: Lê
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulié
authors.forename: Houria
authors.initials: H
authors.lastname: Ichou
authors.forename: Agnès
authors.initials: A
authors.lastname: Bourgeois-Moine
authors.forename: Florence
authors.initials: F
authors.lastname: Damond
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lariven
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Roland
authors.initials: R
authors.lastname: Landman
authors.forename: Philippe
authors.initials: P
authors.lastname: Faucher
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Dominique
authors.initials: D
authors.lastname: Duro
authors.forename: Françoise
authors.initials: F
authors.lastname: Meier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Legac
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourse
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mortier
authors.forename: Marc
authors.initials: M
authors.lastname: Dommergues
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Sophie
authors.initials: S
authors.lastname: Matheron
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
mesh_terms: D000328:Adult; D000069446:Atazanavir Sulfate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007231:Infant, Newborn; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D000069446:Atazanavir Sulfate; D019438:Ritonavir