The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine

Abstract

Reduced levonorgestrel concentrations fromthe levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolismwere linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz-or nevirapinebased antiretroviral therapy (ART), in comparison to ART-na ive women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log(10) C-max and log(10) AUC. CYP2B6 15582C> T was associated with lower log(10) AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log(10) C-max and lower log(10) C-min. Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics.