Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis

Nana Agyemang, Kimberly K. Scarsi, Paxton Baker, Laura M. Smeaton, Anthony T. Podany, Maxine Olefsky, Elizabeth Woolley, Elizabeth Barr, Michelle Pham, Sajeeda Mawlana, Khuanchai Supparatpinyo, Sivaporn Gatechompol, Emilia M. Jalil, Luis Gadama, Sharlaa Badal-Faesen, Marije Van Schalkwyk, Cecelia Kayama, Pablo F. Belaunzaran-Zamudio, Catherine Godfrey, Susan E. CohnRosie Mngqibisa, David W. Haas

Research output: Contribution to journalArticlepeer-review


Objective In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC0-8h). We characterized the pharmacogenetics of these interactions. Methods Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters. Results Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC0-8hvalues similar to controls, while CYP2B6 poor metabolizers had AUC0-8hvalues of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC0-8hvalues similar to controls, while NAT2 slow acetylators had AUC0-8hvalues 36% higher than controls. Conclusion CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalPharmacogenetics and Genomics
Issue number6
StatePublished - Aug 1 2023


  • CYP2B6
  • HIV therapy
  • NAT2
  • efavirenz
  • emergency contraception
  • isoniazid
  • levonorgestrel
  • pharmacogenetics
  • rifampin
  • tuberculosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Genetics(clinical)


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