Correlation between CYP2B6 exonic gene polymorphisms and efavirenz plasma concentrations in Yi ethnic HIV/AIDS patients: a study from Sichuan province, China

Abstract

Polymorphisms in the CYP2B6 Gene significantly impact efavirenz (EFV) metabolism and plasma levels, resulting in variability in both treatment effectiveness and toxicity among individuals. In this study, we aimed to evaluate the relationship between the CYP2B6 polymorphisms and the plasma concentrations of EFV for Yi ethnic HIV positive individuals residing in the province of Sichuan, China. The study consisted of 94 Yi HIV patients receiving antiretroviral therapy (ART) based on efavirenz. All patients had their plasma levels of efavirenz measured, and CYP2B6 gene polymorphisms were detected through sequencing of the gene; statistical analysis, including Chi-square tests, established the relationship between genotype and plasma concentrations of efavirenz and classified those concentrations into therapeutic (1000–4000 ng/mL) and supratherapeutic (> 4000 ng/mL). The median level of EFV in the Yi population was 2550 ng/mL (IQR: 2015–3491.5 ng/mL), with a range of 1009.5-19100 ng/mL. Five polymorphisms in the CYP2B6 gene were identified: 516G > T (allele frequency 0.25), 785A > G (0.3), 1138T > C (0.01), 64C > T (0.03), and 370C > T (0.01). The results showed significant differences in the concentration of EFV based on 516G > T, where the percentage of patients with supratherapeutic concentrations (> 4000 ng/mL) was higher among TT genotype carriers than among wild-type carriers (χ² = 17.00, p = 0.001); 71.43% of patients with the TT genotype had concentrations above 4000 ng/mL compared to only 10.34% of patients with the GG wild-type genotype. The data on the 785A > G variant show that 41.67% of GG carriers had concentrations above 4000 ng/mL, compared with only 12.24% of patients with the AA wild-type genotype. CYP2B6 polymorphisms, specifically the 516G > T and 785A > G, had a major impact on the pharmacokinetics of EFV and therefore led to an increase in plasma concentrations of efavirenz among Yi HIV/AIDS patients. The results also support findings from other studies worldwide that associate these same polymorphisms with decreased enzyme activity and thus decreased ability to metabolize EFV. The unique genetic background of the Yi population underscores the importance of using pharmacogenomics tools specifically designed for this population. CYP2B6 polymorphisms, including specifically the 516G > T variant, are important predictors of plasma concentrations of EFV among Yi HIV positive patients. The 785A > G variant also predicts a higher percentage of patients exceeding the supratherapeutic range and does not affect median plasma concentrations. Dose adjustment guided by genotype may increase treatment response and decrease adverse events in this ethnic population. Not applicable.