title: CYP2B6*6 and CYP2B6*18 Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women.
abstract: Long-term exposure to efavirenz (EFV) measured in hair samples may predict response to antiretroviral treatment (ART). Polymorphisms in CYP2B6 are known to alter EFV levels. The aim of this study was to assess the relationship between CYP2B6 genotype, EFV levels measured in hair, and virological outcomes on ART in a real-world setting. We measured EFV levels in hair from HIV-positive South African females who had been receiving EFV-based treatment for at least 3 months from the South African Black (SAB) (n = 81) and Cape Mixed Ancestry (CMA) (n = 53) populations. Common genetic variation in CYP2B6 was determined in 15 individuals from each population using bidirectional Sanger sequencing. Prioritized variants (n = 16) were subsequently genotyped in the entire patient cohort (n = 134). The predictive value of EFV levels in hair and selected variants in CYP2B6 on virological treatment outcomes was assessed. Previously described alleles (CYP2B6*2, CYP2B6*5, CYP2B6*6, CYP2B6*17, and CYP2B6*18), as well as two novel alleles (CYP2B6*31 and CYP2B6*32), were detected in this study. Compared to noncarriers, individuals homozygous for CYP2B6*6 had ∼109% increased EFV levels in hair (p = .016) and CYP2B6*18 heterozygotes demonstrated 82% higher EFV hair levels (p = .0006). This study confirmed that alleles affecting CYP2B6 metabolism and subsequent EFV exposure are present at significant frequencies in both the SAB and CMA populations. Furthermore, this study demonstrated that the use of hair samples for testing EFV concentrations may be a useful tool in determining long-term drug exposure in resource-limited countries.
authors.affiliation: 1 Department of Genetics, Stellenbosch University , Stellenbosch, South Africa .
authors.forename: Carola R
authors.initials: CR
authors.lastname: Röhrich
authors.affiliation: 1 Department of Genetics, Stellenbosch University , Stellenbosch, South Africa .
authors.forename: Britt I
authors.initials: BI
authors.lastname: Drögemöller
authors.affiliation: 2 Departments of Pharmacy, University of California San Francisco , UCSF, San Francisco, California.
authors.forename: Ogechi
authors.initials: O
authors.lastname: Ikediobi
authors.affiliation: 3 Department of Molecular Biology and Human Genetics, Stellenbosch University , Tygerberg, South Africa .|4 Department of Statistics, University of Western Cape , Bellville, South Africa .
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.affiliation: 5 TC Newman HIV Clinic , Paarl, South Africa .
authors.forename: Nelis
authors.initials: N
authors.lastname: Grobbelaar
authors.affiliation: 1 Department of Genetics, Stellenbosch University , Stellenbosch, South Africa .
authors.forename: Galen E B
authors.initials: GE
authors.lastname: Wright
authors.affiliation: 1 Department of Genetics, Stellenbosch University , Stellenbosch, South Africa .|6 Department of Psychiatry, Stellenbosch University , Tygerberg, South Africa .
authors.forename: Nathaniel
authors.initials: N
authors.lastname: McGregor
authors.affiliation: 1 Department of Genetics, Stellenbosch University , Stellenbosch, South Africa .
authors.forename: Louise
authors.initials: L
authors.lastname: Warnich
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D048588:Benzoxazines / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D017422:Sequence Analysis, DNA; D013019:South Africa; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz