Efavirenz — but not nevirapine — based antiretroviral therapy significantly reduces etonogestrel concentrations among HIV-positive women using subdermal contraceptive implants

Abstract

Objectives: The etonogestrel (ENG) implant is a popular contraceptive method because it is highly effective, increasingly accessible and well tolerated. However, there is concern for decreased contraceptive effectiveness among HIV-infected women due to drug interactions with antiretroviral therapy (ART), particularly efavirenz (EFV). We aimed to characterize the pharmacokinetics of ENG among HIV-infected Ugandan women using EFV- or nevirapine (NVP)-based ART and the ENG implant. Methods: This nonrandomized, parallel group study compared ENG pharmacokinetic parameters in three groups of women; those who were ART naïve, those receiving EFV- or NVP-based ART (N=20 per group). Following implant placement, serum ENG concentrations were assessed at weeks 1, 4, 12 and 24. ART adherence was assessed by serum EFV or NVP concentrations at each visit. Participants on EFV additionally used copper IUDs to ensure pregnancy prevention. ENG and ART concentrations were analyzed using validated LC-MS/MS and HPLC methods, respectively. Results: The groups were similar in age, weight and CD4 count. Data from 58 participants are included; one participant each was excluded from the EFV (ART nonadherence) and NVP (processing error) groups. Geometric mean (GM) ENG concentrations at week 24 were 362, 66 and 341 pg/mL in the ART-naïve, EFV and NVP groups, respectively [GM ratio (90% CI): EFV:ART-naïve,0.18 (0.17–0.20); NVP:ART-naïve, 0.94 (0.90–1.0)]. Conclusions: After 24 weeks of combined use, ENG concentrations were 82% lower among women using EFV-based ART than among ART-naïve women. In contrast, NVP did not significantly change ENG concentrations. These findings are highly concerning for reduced effectiveness of the ENG implant among HIV-infected women receiving EFV-based ART.