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Effect of Antiretroviral Therapy Including Lopinavir/Ritonavir or Efavirenz on Etonogestrel-Releasing Implant Pharmacokinetics in HIV-Positive Women

Vieira, Carolina S. MD, PhD*,†; Bahamondes, Maria V. MD, PhD†,‡; de Souza, Roberto M. PhD§; Brito, Milena B. MD, PhD; Rocha Prandini, Tatiana R. MD*; Amaral, Eliana MD, PhD; Bahamondes, Luis MD, PhD†,‡; Duarte, Geraldo MD, PhD*; Quintana, Silvana M. MD, PhD*; Scaranari, Carolina MD*; Ferriani, Rui A. MD, PhD*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2014 - Volume 66 - Issue 4 - p 378–385
doi: 10.1097/QAI.0000000000000189
Clinical Science

Objective: Data on the interaction between the etonogestrel (ENG) implant and antiretroviral therapy are lacking. We evaluated the effect of 2 highly active antiretroviral therapy (HAART) regimens (1 including efavirenz and the other ritonavir-boosted lopinavir) on the pharmacokinetic (PK) parameters of an ENG-releasing implant in HIV-positive women.

Design: Prospective nonrandomized PK study.

Methods: Forty-five HIV-positive women who desired to use ENG implants were included: 15 had received zidovudine/lamivudine + lopinavir/ritonavir for ≥3 months (LPV/r-based HAART group), 15 had received zidovudine/lamivudine + efavirenz for ≥3 months (EFV-based HAART group), and 15 had not received HAART (non-HAART group). PK parameters were measured using ultra-performance liquid chromatography–mass spectrometry at baseline and 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks after implant placement.

Results: The EFV-based HAART regimen was associated with a reduction in the bioavailability of ENG, which showed decreases of 63.4%, 53.7%, and 70% in the area under the curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) of ENG, respectively, compared with the non-HAART group. The LPV/r-based HAART regimen was associated with an increase in ENG bioavailability, which showed 52%, 60.6%, and 33.8% increases in the ENG AUC, Cmax, and Cmin, respectively, compared with the non-HAART group.

Conclusions: The coadministration of EFV decreased the bioavailability of ENG released from the implant, which could impair contraceptive efficacy. However, the coadministration of LPV/r increased the bioavailability of ENG released from the implant, which suggests that this antiretroviral combination does not impair the ENG implant efficacy.

*Department of Gynecology and Obstetrics, Medical School of Ribeirao Preto, University of São Paulo, São Paulo, Brazil. Avenida Bandeirantes, Ribeirão Preto, São Paulo, Brazil;

National Institute of Hormones and Women's Health, Brazil;

Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil;

§Federal Technological University of Paraná, Campus Cornélio Procópio, Brazil. Avenida Alberto Carazzai, Cornélio Procópio, Paraná, Brazil; and

Department of Gynecology and Obstetrics, Federal University of Bahia. R. Augusto Viana, 1—Canela, CEP: 40110-060, Salvador, Bahia, Brazil.

Correspondence to: Carolina S. Vieira, MD, PhD, Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirao Preto/USP, Av. Bandeirantes 3900, Campus Universitário, Ribeirao Preto—São Paulo, CEP: 14049-900, Brazil (e-mail:

This study was cofunded by the São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP) and the Science and Technology Department of the Brazilian Health Ministry (Grant 2009/53,147-3).

C.S.V., R.A.F., M.B.B., and L.B. give occasional lectures to MSD and Bayer.

All other authors have no conflicts of interest to disclose.

Received December 12, 2013

Accepted March 12, 2014

© 2014 by Lippincott Williams & Wilkins