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The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine
Author(s) -
Neary M,
Lamorde M,
Olagunju A,
Darin KM,
Merry C,
ByakikaKibwika P,
Back DJ,
Siccardi M,
Owen A,
Scarsi KK
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.667
Subject(s) - nevirapine , efavirenz , levonorgestrel , contraceptive implant , pharmacokinetics , pharmacology , cyp2b6 , population , medicine , reverse transcriptase inhibitor , pharmacogenetics , single nucleotide polymorphism , genotype , biology , virology , viral load , antiretroviral therapy , human immunodeficiency virus (hiv) , genetics , cyp3a4 , gene , family planning , cytochrome p450 , metabolism , environmental health , research methodology
Reduced levonorgestrel concentrations from the 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 metabolism were 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 nevirapine‐based antiretroviral therapy (ART), in comparison to ART‐naïve 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.