Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy

J Antimicrob Chemother. 2022 Oct 28;77(11):3144-3152. doi: 10.1093/jac/dkac296.

Abstract

Background: Pharmacokinetic data are lacking for progestin-releasing subdermal contraceptive implants when used with either rilpivirine- or darunavir/ritonavir-based ART.

Objectives: To characterize the pharmacokinetics of etonogestrel or levonorgestrel implants when administered with these ART regimens over 48 weeks.

Patients and methods: Two separate, parallel, three-group, non-randomized, pharmacokinetic studies evaluated either etonogestrel or levonorgestrel in women receiving rilpivirine- or darunavir-based ART compared with women without HIV (control group). Participants on ART were switched to rilpivirine-based ART with a run-in period of 6 weeks or darunavir-based ART with a run-in of 2 weeks prior to implant insertion. Plasma was collected on Day 0, and 1, 4, 12, 24, 36 and 48 weeks post-insertion. Plasma progestin concentrations were compared between ART and control groups by geometric mean ratio (GMR) and 90% CI.

Results: At the primary endpoint of Week 24, progestin concentrations were similar between the rilpivirine and control groups [etonogestrel: 1.18 (0.99-1.37); levonorgestrel: 1.16 (0.97-1.33)]. At Week 24, progestin exposure was higher in the darunavir groups compared with the control group [etonogestrel: 2.56 (1.69-3.28); levonorgestrel: 1.89 (1.38-2.29)]. Results remained consistent through to Week 48. No differences in etonogestrel-related adverse events were observed, but both ART groups experienced more menstrual abnormalities versus the control group with levonorgestrel.

Conclusions: Etonogestrel and levonorgestrel concentrations were not altered by rilpivirine-based ART. Although progestin concentrations were higher in the ART groups containing ritonavir-boosted darunavir, no implant-related serious adverse events were observed. Both progestin-releasing implants are an appropriate contraceptive option with either rilpivirine- or darunavir/ritonavir-based ART.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Contraceptive Agents
  • Darunavir / adverse effects
  • Female
  • HIV Infections* / drug therapy
  • Humans
  • Levonorgestrel* / adverse effects
  • Levonorgestrel* / pharmacokinetics
  • Progestins
  • Rilpivirine / adverse effects
  • Ritonavir

Substances

  • etonogestrel
  • Darunavir
  • Levonorgestrel
  • Rilpivirine
  • Ritonavir
  • Progestins
  • Contraceptive Agents