CYP2B6*6andCYP2B6*18Predict 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.

A validated liquid chromatography/tandem mass spectrometry method for the analysis of efavirenz in 0.2 mg hair samples from human immunodeficiency virus infected patients

“…The median EFV concentration in the hair samples was reported to be 5.60 ng/mg (interquartile range (IQR): 3.93–7.06 ng/mg). In this case, EFV levels in hair were not found to be associated with virologic response …”

“…The Huang et al method has been used for the determination of EFV levels in hair in the context of other studies; however, the amount of published data regarding EFV levels in hair remains limited. Moreover, there is only one study that reports EFV levels in hair samples collected from South Africans . In that study hair samples ( n = 134) collected from HIV‐infected South African females were sent to an international laboratory for the analysis and quantification of EFV.…”

“…The Huang et al 21 method has been used for the determination of EFV levels in hair in the context of other studies; 11,18,23,24 however, the amount of published data regarding EFV levels in hair remains limited. Moreover, there is only one study that reports EFV levels in hair samples collected from South Africans.…”

“…Moreover, there is only one study that reports EFV levels in hair samples collected from South Africans. 24 In that study hair samples (n = 134) collected from HIV-infected South African females were sent to an international laboratory for the analysis and quantification of EFV. The median EFV concentration in the hair samples was reported to be 5.60 ng/mg (interquartile range (IQR):…”

“…In this case, EFV levels in hair were not found to be associated with virologic response. 24 There is a need for the development of validated methods for the analysis of ARVs in hair in South Africa to complement current methods of TDM and to provide objective measures of assessing long-term adherence. Additionally, it is also possible to improve on some aspects of the method published by Huang et al 21…”