title: Atazanavir pharmacokinetics with and without tenofovir during pregnancy.
abstract: BACKGROUND
  Few data are available describing atazanavir exposure during pregnancy, especially when used in combination with tenofovir, whose coadministration with atazanavir results in decreased atazanavir exposure.
  
  
  METHODS
  International Maternal Pediatric Adolescent AIDS Clinical Trials 1026 s is an ongoing, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included 2 cohorts receiving atazanavir/ritonavir 300 mg/100 mg once daily, either with or without tenofovir.
  
  
  METHODS
  Intensive steady-state 24-hour pharmacokinetic profiles were performed during the third trimester and at 6-12 weeks postpartum. Atazanavir was measured by reverse-phase high-performance liquid chromatography (detection limit 0.047 mcg/mL). Pharmacokinetic targets were the estimated 10th percentile atazanavir area under the concentration versus time curve [(AUC): 29.4 mcg · hr · mL-1] in nonpregnant historical controls (mean AUC = 57 mcg · hr · mL-1) and a trough concentration of 0.15 mcg/mL, the concentration target used in therapeutic drug monitoring programs.
  
  
  RESULTS
  Median atazanavir AUC was reduced during the third trimester compared with postpartum for subjects not receiving tenofovir (41.9 vs. 57.9 mcg · hr · mL-1, P = 0.02) and for subjects receiving tenofovir (28.8 vs. 39.6 mcg · hr · mL-1, P = 0.04). During the third trimester, AUC was below the target in 33% (6 of 18) of women not receiving tenofovir and 55% (11 of 20) of women receiving tenofovir. Trough concentration was below the target in 6% (1 of 18) of women not receiving tenofovir and 15% (3 of 20) of women receiving tenofovir. The median (range) ratio of cord blood/maternal atazanavir concentration in 29-paired samples was 0.18 (0-0.45).
  
  
  CONCLUSIONS
  Atazanavir exposure is reduced by pregnancy and by concomitant tenofovir use. A dose increase of atazanavir/ritonavir to 400 mg/100 mg may be necessary in pregnant women to ensure atazanavir exposure equivalent to that seen in nonpregnant adults.
authors.affiliation: Department of Pediatrics, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Alice M
authors.initials: AM
authors.lastname: Stek
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hu
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
authors.forename: Steven S
authors.initials: SS
authors.lastname: Rossi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hawkins
authors.forename: Michael
authors.initials: M
authors.lastname: Basar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Read
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir