title: Atazanavir exposure is effective during pregnancy regardless of tenofovir use.
abstract: BACKGROUND
  We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir.
  
  
  METHODS
  This was a non-randomized, open-label, multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres. HIV-infected pregnant women treated with boosted atazanavir (300/100 mg or 400/100 mg atazanavir/ritonavir) as part of their combination antiretroviral therapy (cART) were included in the study. 24 h pharmacokinetic curves were recorded in the third trimester and postpartum. Collection of a cord blood and maternal sample at delivery was optional.
  
  
  RESULTS
  31 patients were included in the analysis, 21/31 patients used tenofovir as part of cART. Median (range) gestational age at delivery was 39 weeks (36-42). Approaching delivery 81% (25 patients) had an HIV viral load <50 copies/ml, all <1,000 copies/ml. Least squares means ratios (90% CI) of atazanavir pharmacokinetic parameters third trimester/postpartum were: 0.66 (0.57, 0.75) for AUC0-24h, 0.70 (0.61, 0.80) for Cmax and 0.59 (0.48, 0.72) for C24h. No statistical difference in pharmacokinetic parameters was found between patients using tenofovir versus no tenofovir. None of the patients showed atazanavir concentrations <0.15 mg/l (target for treatment-naive patients). One baby had a congenital abnormality, which was not likely to be related to atazanavir/ritonavir use. None of the children were HIV-infected.
  
  
  CONCLUSIONS
  Despite 34% lower atazanavir exposure during pregnancy, atazanavir/ritonavir 300/100 mg once daily generates effective concentrations for protease inhibitor (PI)-naive patients, even if co-administered with tenofovir. For treatment-experienced patients (with relevant PI resistance mutations) therapeutic drug monitoring of atazanavir should be considered to adapt the atazanavir/ritonavir dose on an individual basis.  ClinicalTrials.gov number NCT00825929.
authors.affiliation: Radboud University Medical Center, Nijmegen, the Netherlands. angela.colbers@radboudumc.nl.
authors.forename: Angela
authors.initials: A
authors.lastname: Colbers
authors.forename: David
authors.initials: D
authors.lastname: Hawkins
authors.forename: Carmen
authors.initials: C
authors.lastname: Hidalgo-Tenorio
authors.forename: Marchina
authors.initials: M
authors.lastname: van der Ende
authors.forename: Andrea
authors.initials: A
authors.lastname: Gingelmaier
authors.forename: Katharina
authors.initials: K
authors.lastname: Weizsäcker
authors.forename: Kabamba
authors.initials: K
authors.lastname: Kabeya
authors.forename: Graham
authors.initials: G
authors.lastname: Taylor
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: John
authors.initials: J
authors.lastname: Lambert
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Christoph
authors.initials: C
authors.lastname: Wyen
authors.forename: S Tariq
authors.initials: ST
authors.lastname: Sadiq
authors.forename: Jelena
authors.initials: J
authors.lastname: Ivanovic
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: David
authors.initials: D
authors.lastname: Burger
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D000069446:Atazanavir Sulfate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005865:Gestational Age; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D006801:Humans; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068698:Tenofovir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D019438:Ritonavir