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Clin Infect Dis. 2016 Mar 15;62(6):675-682. doi: 10.1093/cid/civ1001. Epub 2015 Dec 8.

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

Author information

1
Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha.
2
Center for Global Health.
3
Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
4
Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
5
Department of Molecular and Clinical Pharmacology, University of Liverpool, United Kingdom.
6
Department of Medicine, Trinity College Dublin, Ireland.

Abstract

BACKGROUND:

Levonorgestrel subdermal implants are preferred contraceptives with an expected failure rate of <1% over 5 years. We assessed the effect of efavirenz- or nevirapine-based antiretroviral therapy (ART) coadministration on levonorgestrel pharmacokinetics.

METHODS:

This nonrandomized, parallel group, pharmacokinetic evaluation was conducted in three groups of human immunodeficiency virus-infected Ugandan women: ART-naive (n = 17), efavirenz-based ART (n = 20), and nevirapine-based ART (n = 20). Levonorgestrel implants were inserted at baseline in all women. Blood was collected at 1, 4, 12, 24, 36, and 48 weeks. The primary endpoint was week 24 levonorgestrel concentrations, compared between the ART-naive group and each ART group by geometric mean ratio (GMR) with 90% confidence interval (CI). Secondary endpoints included week 48 levonorgestrel concentrations and unintended pregnancies.

RESULTS:

Week 24 geometric mean levonorgestrel concentrations were 528, 280, and 710 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.53; 90% CI, .50, .55 and nevirapine: ART-naive GMR, 1.35; 90% CI, 1.29, 1.43). Week 48 levonorgestrel concentrations were 580, 247, and 664 pg/mL in the ART-naive, efavirenz, and nevirapine groups, respectively (efavirenz: ART-naive GMR, 0.43; 90% CI, .42, .44 and nevirapine: ART-naive GMR, 1.14; 90% CI, 1.14, 1.16). Three pregnancies (3/20, 15%) occurred in the efavirenz group between weeks 36 and 48. No pregnancies occurred in the ART-naive or nevirapine groups.

CONCLUSIONS:

Within 1 year of combined use, levonorgestrel exposure was markedly reduced in participants who received efavirenz-based ART, accompanied by contraceptive failures. In contrast, nevirapine-based ART did not adversely affect levonorgestrel exposure or efficacy.

CLINICAL TRIALS REGISTRATION:

NCT01789879.

KEYWORDS:

contraceptive implant; efavirenz; levonorgestrel; nevirapine; unintended pregnancy

PMID:
26646680
PMCID:
PMC4772838
DOI:
10.1093/cid/civ1001
[Indexed for MEDLINE]
Free PMC Article

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