A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy - 26/07/24
Abstract |
Background |
Concomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant led to 82% lower etonogestrel exposure when compared with women who do not receive antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations that demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of 2 etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy.
Objective |
This study compared the rate of ovulation and etonogestrel pharmacokinetics among women on efavirenz-based antiretroviral therapy who received 2 etonogestrel implants (136 mg; double implant group) in comparison with those who received 1 etonogestrel implant (68 mg; control group).
Study Design |
This randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for the treatment of HIV. Participants were randomized 1:1 to the double implant or control group, and the etonogestrel implant(s) were placed in the same arm at enrollment. All participants used a copper intrauterine device to prevent pregnancy. Ovulation was evaluated by weekly serum progesterone concentrations measured over 4 consecutive weeks at months 3 (weeks 9–12), 6 (weeks 21–24), and 12 (weeks 45–48). Progesterone concentrations >3 ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher’s exact tests for each month and generalized estimating equations over 48 weeks. Plasma was collected at day 3 and weeks 1, 4, 12, 24, 36, and 48 after implant placement and analyzed using a validated liquid chromatography–triple quadrupole mass spectrometry method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range) and compared between groups by geometric mean ratio with 90% confidence intervals.
Results |
All participants (n=72) were cisgender Ugandan women with a median age of 31 years (interquartile range, 29–36), and 36 participants were enrolled in each study group. Two participants in the control group discontinued the trial; 1 at week 1 because of undetected pregnancy at entry and another at week 45 because of clinically significant depression. There were 47 ovulations over 104 person-months (45%) in 25 of 34 participants in the control group, and 2 ovulations over 108 person-months (2%) in 2 of 36 participants in the double implant group (month 3: 11 [31%] vs 0 [0%]; month 6: 17 [49%] vs 0 [0%]; month 12: 19 [56%] vs 2 [6%], respectively; all P<.001). The odds of ovulation were reduced by 97.7% (95% confidence interval, 90.1–99.5) in the double implant group over 48 weeks. At each time point, etonogestrel concentration was more than 2-fold higher in the double implant group than in the controls (geometric mean ratio, 2.30–2.83) with a geometric mean ratio of 2.83 (90% confidence interval, 1.89–3.35) at week 48. There were no differences in the adverse events between groups and no participant discontinued because of adverse events.
Conclusion |
Over 48 weeks of combined use, placing 2 etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure when compared with 1 etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel during efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.
Le texte complet de cet article est disponible en PDF.Key words : contraceptive implant, efavirenz, etonogestrel, HIV
Plan
C.A.C. reports receiving research funding from Gilead Sciences for several studies from 2016 to current and from Merck/Organon for this study from 2018 to current. S.N., I.K., L.A.M., and K.K.S. also report receiving funding from Merck/Organon for this study from 2018 to current. K.K.S. reports receiving funding to her institution for another study from Merck/Organon from 2020 to current. M.M.P. reports serving as an employee of Merck & Co. None of the other authors have conflict of interest to disclose. |
|
This study was funded by the Organon/Merck Investigator Initiated Studies Program under grant number 55906. Organon/Merck had no role in the study design, in the collection, analysis, or interpretation of the data, or in the writing of the manuscript. |
|
This study was registered with ClinicalTrials.gov on September 14, 2017. The date of initial participant enrollment was February 19, 2019. The clinical trial identification number is NCT03282799 (NCT03282799). |
|
All of the de-identified individual participant data collected during the trial and the study protocol and informed consent forms will be available immediately following publication without end date to anyone who wishes to access the data. |
|
This study was presented virtually at the Conference on Retroviruses and Opportunistic Infections 2022, Boston, MA, February 12–16, 2022. |
|
Cite this article as: Chappell CA, Lamorde M, Nakalema S, et al. A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy. Am J Obstet Gynecol 2024;231:242.e1-9. |
Vol 231 - N° 2
P. 242.e1-242.e9 - août 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?