title: Pharmacogenetics of efavirenz discontinuation for reported central nervous system symptoms appears to differ by race.
abstract: Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation.
  
  
  
  Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification.
  
  
  
  Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks.
  
  
  
  Slow metabolizer genotypes were associated significantly with efavirenz discontinuation for reported CNS symptoms. This association was considerably stronger in Whites than in Blacks.
authors: aDepartment of Medicine bVanderbilt Technologies for Advanced Genomics Analysis and Research Design (VANGARD) cVanderbilt Technologies for Advanced Genomics (VANTAGE), Vanderbilt University Medical Center dDepartment of Medicine, Pharmacology, Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine eDepartment of Neuroscience & Pharmacology, Meharry Medical College, Nashville, Tennessee, USA.
authors: Paul
authors: P
authors: Leger
authors: Sanika
authors: S
authors: Chirwa
authors: Megan
authors: M
authors: Turner
authors: Danielle M
authors: DM
authors: Richardson
authors: Paxton
authors: P
authors: Baker
authors: Michael
authors: M
authors: Leonard
authors: Husamettin
authors: H
authors: Erdem
authors: Lana
authors: L
authors: Olson
authors: David W
authors: DW
authors: Haas
mesh_terms: D000328:Adult; D000480:Alkynes; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000009:adverse effects*; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D013250:Steroid Hydroxylases / Q000235:genetics*; D028761:Withholding Treatment
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C029009:steroid hormone 7-alpha-hydroxylase; C098320:efavirenz