Efavirenz decreases etonogestrel exposure: A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy

Catherine A. Chappell, Mohammed Lamorde, Shadia Nakalema, Beatrice A. Chen, Hope Mackline, Sharon A. Riddler, Susan E. Cohn, Kristin M. Darin, Sharon L. Achilles, Kimberly K. Scarsi

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Objectives: The primary objective of this study was to characterize the pharmacokinetics of etonogestrel (ENG) released from a contraceptive implant in Ugandan women living with HIV who were receiving efavirenz (EFV) or nevirapine (NVP)-based antiretroviral therapy (ART), compared with ART-naive women over 24 weeks. Design: Nonrandomized, parallel-group study with three arms: ART-naive, NVP, or EFV-based ART (N==20/group). Methods: Sparse pharmacokinetic sampling of ENG, NVP, or EFV were performed at screening, entry, and then 1, 4, 12, and 24-week postimplant insertion. The primary endpoint was ENG concentrations at week 24, compared between the ART-naive group and each ART group, using geometric mean ratio (GMR) with 90% confidence intervals. Results: Sixty participants competed the 24-week study and data from 58 participants are included; one participant each was excluded from the NVP group and EFV group because of a sample processing error and ART nonadherence, respectively. At week 24, geometric mean ENG was 362, 341, and 66=pg/ml in the ART-naive, NVP, and EFV groups, respectively [GMR: NVP=:ART-naive 0.94 (0.90-1.01); EFV=:ART-naive 0.18 (0.17-0.20)]. NVP and EFV concentrations were lower at week 24 compared to preimplant [NVP: geometric mean 5.7 versus 6.8=mg/l, respectively, GMR 0.84 (0.83-0.85); EFV: geometric mean 3.6 versus 4.9=mg/l, respectively, GMR 0.73 (0.69-0.80)]. Conclusion: After 24 weeks of combined use, ENG exposure was 82% lower in women using EFV-based ART compared with ART-naive women. In contrast, NVP did not significantly impact ENG exposure. These results raise concerns about reduced effectiveness of implantable contraception for women taking EFV-based ART.

Original languageEnglish (US)
Pages (from-to)1965-1972
Number of pages8
JournalAIDS
Volume31
Issue number14
DOIs
StatePublished - Sep 10 2017

Keywords

  • antiretroviral therapy
  • contraceptive implant
  • drug-drug interaction
  • efavirenz
  • etonogestrel
  • family planning
  • nevirapine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Chappell, C. A., Lamorde, M., Nakalema, S., Chen, B. A., Mackline, H., Riddler, S. A., Cohn, S. E., Darin, K. M., Achilles, S. L., & Scarsi, K. K. (2017). Efavirenz decreases etonogestrel exposure: A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS, 31(14), 1965-1972. https://doi.org/10.1097/QAD.0000000000001591