Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women

J Acquir Immune Defic Syndr. 2014 Aug 1;66(4):378-85. doi: 10.1097/QAI.0000000000000189.

Abstract

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Benzoxazines / therapeutic use*
  • Biological Availability
  • Contraceptive Agents, Female / pharmacokinetics
  • Cyclopropanes
  • Desogestrel / pharmacokinetics*
  • Drug Combinations
  • Drug Implants
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lopinavir / therapeutic use*
  • Ritonavir / therapeutic use*
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Contraceptive Agents, Female
  • Cyclopropanes
  • Drug Combinations
  • Drug Implants
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • etonogestrel
  • Desogestrel
  • efavirenz
  • Ritonavir