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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

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efavirenz
Nevirapine
Contraception
Pharmacokinetics
Therapeutics
Group Psychotherapy
etonogestrel

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Efavirenz decreases etonogestrel exposure : A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. / Chappell, Catherine A.; Lamorde, Mohammed; Nakalema, Shadia; Chen, Beatrice; Mackline, Hope; Riddler, Sharon; Cohn, Susan; Darin, Kristin; Achilles, Sharon; Scarsi, Kimberly K.

In: AIDS, Vol. 31, No. 14, 10.09.2017, p. 1965-1972.

Research output: Contribution to journalArticle

Chappell, CA, Lamorde, M, Nakalema, S, Chen, B, Mackline, H, Riddler, S, Cohn, S, Darin, K, Achilles, S & Scarsi, KK 2017, 'Efavirenz decreases etonogestrel exposure: A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy', AIDS, vol. 31, no. 14, pp. 1965-1972. https://doi.org/10.1097/QAD.0000000000001591
Chappell, Catherine A. ; Lamorde, Mohammed ; Nakalema, Shadia ; Chen, Beatrice ; Mackline, Hope ; Riddler, Sharon ; Cohn, Susan ; Darin, Kristin ; Achilles, Sharon ; Scarsi, Kimberly K. / Efavirenz decreases etonogestrel exposure : A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. In: AIDS. 2017 ; Vol. 31, No. 14. pp. 1965-1972.
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title = "Efavirenz decreases etonogestrel exposure: A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy",
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.",
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T2 - A pharmacokinetic evaluation of implantable contraception with antiretroviral therapy

AU - Chappell, Catherine A.

AU - Lamorde, Mohammed

AU - Nakalema, Shadia

AU - Chen, Beatrice

AU - Mackline, Hope

AU - Riddler, Sharon

AU - Cohn, Susan

AU - Darin, Kristin

AU - Achilles, Sharon

AU - Scarsi, Kimberly K

PY - 2017/9/10

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N2 - 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.

AB - 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.

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KW - contraceptive implant

KW - drug-drug interaction

KW - efavirenz

KW - etonogestrel

KW - family planning

KW - nevirapine

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