title: Low level of efavirenz in HIV-1-infected Thai adults is associated with the CYP2B6 polymorphism.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 (HIV-1) infections with a plasma efavirenz concentration of <1,000 ng/mL appear to have a high risk for the emergence of drug resistance. In the present study, we assessed the influence of the CYP2B6 polymorphism on the plasma efavirenz level.
  
  
  METHODS
  CYP2B6 T18492C (rs2279345) in 149 HIV-infected Thai adults were genotyped. Plasma efavirenz concentrations 12 h after dosing were measured using a validated high-performance liquid chromatography. The relationship between the plasma efavirenz level and the CYP2B6 T18492C polymorphism were analysed.
  
  
  RESULTS
  Among the 149 patients, the frequency of T18492C heterozygous (T/C) and homozygous mutant (C/C) was 38.26 % (n = 57) and 6.04 % (n = 9), respectively. In the entire cohort, the median efavirenz plasma concentration was 2,410 ng/mL [interquartile range (IQR) 1,460-4,120 ng/mL]. The plasma efavirenz concentration for patients with 18492CC (1,200 ng/mL, IQR 1,050-1,990 ng/mL) or 18492TC (1,900 ng/mL, IQR 1,320-2,510 ng/mL) genotypes were significantly lower than those with homozygous wild type (3,380 ng/mL, IQR 2,040-5,660 ng/mL), P-value < 0.001.
  
  
  CONCLUSIONS
  The CYP2B6 T18492C polymorphism was significantly associated with lower efavirenz concentrations compared to those with homozygous wild type in HIV-1 infections. The genetic polymorphism CYP2B6 T18492C may be useful for the optimised efavirenz dose. Further studies in the clinical setting will need to be conducted before such an approach can be recommended for widespread use.
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, chonlaphat_suk@hotmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Sukasem
authors.forename: W
authors.initials: W
authors.lastname: Manosuthi
authors.forename: N
authors.initials: N
authors.lastname: Koomdee
authors.forename: S
authors.initials: S
authors.lastname: Santon
authors.forename: T
authors.initials: T
authors.lastname: Jantararoungtong
authors.forename: S
authors.initials: S
authors.lastname: Prommas
authors.forename: M
authors.initials: M
authors.lastname: Chamnanphol
authors.forename: A
authors.initials: A
authors.lastname: Puangpetch
authors.forename: S
authors.initials: S
authors.lastname: Sungkanuparph
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010949:Plasma / Q000737:chemistry*; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz