Pharmacogenomics and Personalized Medicine (Jul 2021)

Influence of SULT1A1*2 Polymorphism on Plasma Efavirenz Concentration in Thai HIV-1 Patients

  • Chamnanphon M,
  • Sukprasong R,
  • Gaedigk A,
  • Manosuthi W,
  • Chariyavilaskul P,
  • Wittayalertpanya S,
  • Koomdee N,
  • Jantararoungtong T,
  • Puangpetch A,
  • Sukasem C

Journal volume & issue
Vol. Volume 14
pp. 915 – 926

Abstract

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Monpat Chamnanphon,1,2,* Rattanaporn Sukprasong,3,4,* Andrea Gaedigk,5,6 Weerawat Manosuthi,7 Pajaree Chariyavilaskul,2 Supeecha Wittayalertpanya,2 Napatrupron Koomdee,3,4 Thawinee Jantararoungtong,3,4 Apichaya Puangpetch,3,4 Chonlaphat Sukasem3,4 1Department of Pathology, Faculty of Medicine, Srinakharinwirot University, Nakornnayok, Thailand; 2Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 4Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand; 5Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children’s Mercy Kansas City, Kansas City, MO, USA; 6School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA; 7Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand*These authors contributed equally to this workCorrespondence: Chonlaphat SukasemDivision of Pharmacogenetics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, ThailandTel +66-2-200-4331Fax +66-2-200-4332Email [email protected]: Plasma efavirenz (EFV) concentrations within therapeutic levels are essential to successfully treat patients suffering from human immunodeficiency virus (HIV) type 1. In addition to the drug-metabolizing enzyme CYP2B6, other phase II drug-metabolizing enzymes and transporters may have an important role in the pharmacokinetics of EFV. Thus, the influence of phase II drug-metabolizing enzymes and drug transporters on plasma EFV levels was investigated in Thai HIV patients receiving EFV.Patients and Methods: Genotyping was performed by TaqMan® real-time PCR in 149 HIV-infected Thai adults, and plasma efavirenz concentration was measured by a validated high-performance liquid chromatography in 12 hours after dosing steady-state plasma samples at week 12 and 24.Results: Patients with three or more copies of SULT1A1 had significantly lower median plasma EFV concentrations than those carrying two copies at week 12 (p=0.046) and SULT1A1*2 (c.638G>A) carriers had significantly lower median plasma EFV concentrations compared to those not carrying the variant at week 24 (p=0.048). However, no significant association was found after adjusting for CYP2B6 genotype.Conclusion: Genetic variation in a combination of SULT1A1*2 and SULT1A1 copy number may contribute to variability in EFV metabolism and thereby may impact drug response. The influence of a combination between the SULT1A1 and CYP2B6 genotype on EFV pharmacokinetics should be further investigated in a larger study population.Keywords: phase II drug-metabolizing enzymes, transporter genes, efavirenz, HIV-1, Thai

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