Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy. (5th September 2022)

• Record Type: Journal Article
• Authors: Nakalema, Shadia; Chappell, Catherine A; Pham, Michelle; Byakika-Kibwika, Pauline; Kaboggoza, Julian; Walimbwa, Stephen I; Musaazi, Joseph; Nakijoba, Ritah; Mbabazi, Leah; Kyohairwe, Isabella; Nassiwa, Sylvia; Jeppson, Jeffrey; Winchester, Lee; Siccardi, Marco; Fletcher, Courtney V; Scarsi, Kimberly K; Lamorde, Mohammed
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 77:Number 11(2022)
• Page Start: 3144
• Page End: 3152
• Publication Date: 2022-09-05
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkac296
• Languages: English
• ISSNs: 0305-7453

Abstract

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.