Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188

J Acquir Immune Defic Syndr. 2010 Dec;55(4):473-82. doi: 10.1097/QAI.0b013e3181eb5ff5.

Abstract

Background: Pharmacokinetic (PK) interactions between lopinavir/ritonavir (LPV/r) and transdermally delivered ethinyl estradiol (EE) and norelgestromin (NGMN) are unknown.

Methods: Using a standard noncompartmental PK analysis, we compared EE area under the time-concentration curve (AUC) and NGMN AUC during transdermal contraceptive patch administration in HIV-1-infected women on stable LPV/r to a control group of women not on highly active antiretroviral therapy (HAART). In addition, EE AUC after a single dose of a combination oral contraceptive pill including EE and norethindrone was measured before patch placement and was compared with patch EE AUC in both groups. Contraceptive effects on LPV/r PKs were estimated by measuring LPV/r AUC at baseline and during week 3 of patch administration.

Results: Eight women on LPV/r, and 24 women in the control group were enrolled. Patch EE median AUC0-168 h was 45% lower at 6010.36 pg·h·mL in those on LPV/r versus 10911.42 pg·h·mL in those on no HAART (P = 0.064). Pill EE median AUC0-48 hours was similarly 55% lower at 344.67 pg·h·mL in those on LPV/r versus 765.38 pg·h·mL in those on no HAART (P = 0.003). Patch NGMN AUC0-168 h however, was 138.39 ng·h·mL, 83% higher in the LPV/r group compared with the control AUC of 75.63 ng·h·mL (P = 0.036). After 3 weeks on the patch, LPV AUC0-8 h decreased by 19%, (P = 0.156).

Conclusions: Although PKs of contraceptive EE and NGMN are significantly altered with LPV/r, the contraceptive efficacy of the patch is likely to be maintained. Larger studies are indicated to fully assess contraceptive efficacy versus risks of the transdermal contraceptive patch when co-administered with protease inhibitors.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / pharmacokinetics*
  • Drug Combinations
  • Drug Interactions
  • Estrogens / administration & dosage
  • Estrogens / pharmacokinetics*
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1*
  • Humans
  • Lopinavir
  • Middle Aged
  • Norgestrel / administration & dosage
  • Norgestrel / analogs & derivatives*
  • Norgestrel / pharmacokinetics
  • Oximes / administration & dosage
  • Oximes / pharmacokinetics
  • Pyrimidinones / administration & dosage
  • Pyrimidinones / pharmacokinetics*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacokinetics*
  • Transdermal Patch
  • United States

Substances

  • Contraceptives, Oral, Combined
  • Drug Combinations
  • Estrogens
  • HIV Protease Inhibitors
  • Oximes
  • Pyrimidinones
  • Lopinavir
  • Norgestrel
  • Ethinyl Estradiol
  • Ritonavir
  • norelgestromin

Grant support