Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks

Abstract

Women receiving efavirenz-based antiretroviral therapy plus a contraceptive implant had significantly lower levonorgestrel pharmacokinetics than women not receiving antiretroviral therapy. An unexpected high pregnancy rate (3/20, 15%) occurred in the efavirenz group, highlighting the clinical significance of this interaction.

Strengthening implant provision and acceptance in South Africa with the ‘Any woman, any place, any time’ approach: An essential step towards reducing unintended pregnancies

“…[74][75][76] Interactions between efavirenz and Jadelle appear even more pronounced than with Implanon. [77,78] Women using an implant, who are also taking efavirenz, have higher pregnancy rates than those taking other antiretrovirals. The higher adherence to the implant, however, when compared with shortacting methods including injectable progestins, [79,80] means that despite this drug interaction, the implant remains highly effective in these women -more so than short-acting alternatives.…”

Correlation between Co-Therapy of Efavirenz-Based ART and Pregnancy among HIV-Positive Women on Hormonal Contraceptive Implants at TASO Tororo-Uganda: A Retrospective Review

“…Most of the pregnancies occurred on average 16 months after implants insertion suggesting a more rapid than expected decrease in levonorgestrel, which is expected to protect from pregnancy up to 5 years after insertion. In Uganda, one study showed that efavirenz reduces blood level of levonorgestrel and resulting to a higher contraceptive failure rate among women on both efavirenz based regimen and implants [3]. This strengthens the evidence that women on EFV-based regimens desiring contraception may need to be cautioned about a potential increased risk of pregnancy with use of HCI.…”

“…It is estimated that up to 14% of women living with HIV in SSA use implants [1]. However, there are controversial findings about potential interactions between hormonal contraceptive implants (HCI) and antiretroviral therapy (ART) [2][3][4]. In Swaziland, 12.4% of women taking efavirenz (EFV)-based regimens while onlevonorgestrel implant became pregnant, and EFV co-therapy were the only variable significantly correlated with pregnancy [1].…”

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol‐containing oral contraceptive in healthy adult women

“…EO and LNG are primarily metabolized by the CYP pathway and are impacted by agents that induce or inhibit these metabolizing enzymes. Coadministration with agents known to induce this metabolic pathway may reduce plasma concentrations of these exogenous hormones, permitting escape ovulation and potentially resulting in contraceptive failure 9, 10. Since EO and LNG are not known inhibitors or inducers of CYP or glucuronyl transferase activity, it is unlikely that either would impact the PK of CAB.…”