CYP2B6 516G>T (rs3745274) and Smoking Status Are Associated With Efavirenz Plasma Concentration in a Serbian Cohort of HIV Patients

Background: Genetic factors have been associated with efavirenz (EFV) plasma concentrations in different populations. In this study, we investigated the effects of CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), CAR c.152-1089T>C (rs3003596), and smoking status in a cohort of Serbian patients with HIV. Methods: Patients with HIV positive, all whites, were recruited from the HIV/AIDS Center at the Infectious and Tropical Diseases Hospital, University of Belgrade Teaching Hospital, Belgrade, Serbia. Mid dose (10-14 hours after dose) EFV plasma concentration was determined using a validated liquid chromatography/tandem mass spectrometry method. Genotyping for CYP2B6 516G>T (rs3745274), CYP2B6 c. 485-18C. T (rs4803419), CAR c.540C>T (rs2307424), and CAR c.152-1089T>C (rs3003596) was conducted using allelic discrimination real-time polymerase chain reaction assay. One-way analysis of variance, Mann-Whitney test, Pearson or Spearman correlation, and multiple linear regression were used for data analysis. Results: Minor allele frequencies were similar to frequencies reported in other European populations. The overall mean (95% confidence interval) plasma EFV concentration was 2800 ng/mL (2460-3140). Significant differences between patients based on CYP2B6 516G>T (rs3745274) genotypes were observed: GG (n = 60), 2320 (range, 2160-2480) ng/mL; GT (n = 30), 3230 (range, 2790-3670) ng/mL; and TT (n = 2), 10,700 (range, 6170-15,300) ng/mL (P = 2.0 x 10(-17)). In multivariate linear regression analysis, CYP2B6 516G>T (rs3745274) [beta = 1770 (1230 to 2310) ng/mL, P < 0.0001] and smoking status [beta = -464 (-1250 to -43.3) ng/mL, P = 0.038] were independently associated with plasma EFV concentrations. Conclusions: The effects of CYP2B6 516G>T (rs3745274) and smoking status on EFV plasma concentration in the Serbian population have been established for the first time.