title: Therapeutic drug monitoring and pharmacogenetic study of HIV-infected ethnic Chinese receiving efavirenz-containing antiretroviral therapy with or without rifampicin-based anti-tuberculous therapy.
abstract: OBJECTIVE
  Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.
  
  
  METHODS
  HIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively.
  
  
  RESULTS
  From October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33-0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97-9.59) in multivariate analysis.
  
  
  CONCLUSIONS
  Despite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Kuan-Yeh
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan ; Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsin-Yun
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Mao-Song
authors.initials: MS
authors.lastname: Tsai
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Bing-Ru
authors.initials: BR
authors.lastname: Wu
authors.affiliation: Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Sue-Yo
authors.initials: SY
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sui-Yuan
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan ; China Medical University, Taichung, Taiwan.
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D048588:Benzoxazines / Q000097:blood / Q000627:therapeutic use*; D001835:Body Weight; D002681:China; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012293:Rifampin / Q000627:therapeutic use*; D014376:Tuberculosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz; D012293:Rifampin