Atazanavir pharmacokinetics with and without tenofovir during pregnancy

Mark Mirochnick, Brookie M. Best, Alice M. Stek, Edmund V. Capparelli, Chengcheng Hu, Sandra K. Burchett, Steven S. Rossi, Elizabeth Hawkins, Michael Basar, Elizabeth Smith, Jennifer S. Read

Research output: Contribution to journalArticle

62 Scopus citations

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. Design: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s 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-1). Pharmacokinetic targets were the estimated 10th percentile atazanavir area under the concentration versus time curve [(AUC): 29.4 mcg•hr•mL] in nonpregnant historical controls (mean AUC = 57 mcg•hr•mL-1) and a trough concentration of 0.15 mcg/mL-1, 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.

Original languageEnglish (US)
Pages (from-to)412-419
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume56
Issue number5
DOIs
StatePublished - Apr 15 2011

Keywords

  • HIV
  • atazanavir
  • mother to child transmission
  • pharmacokinetics
  • pregnancy
  • tenofovir

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Mirochnick, M., Best, B. M., Stek, A. M., Capparelli, E. V., Hu, C., Burchett, S. K., Rossi, S. S., Hawkins, E., Basar, M., Smith, E., & Read, J. S. (2011). Atazanavir pharmacokinetics with and without tenofovir during pregnancy. Journal of Acquired Immune Deficiency Syndromes, 56(5), 412-419. https://doi.org/10.1097/QAI.0b013e31820fd093