| Objective: To study the difference of plasma concentration of different doses of efavirenz taken by Yi ethnic group with HIV/AIDS and the factors affecting the plasma concentration.To explore the relationship between CYP2B6 gene polymorphism and plasma concentration of efavirenz in Yi ethnic group.To explore the feasibility of reducing the amount of efavirenz and further optimize the antiviral therapy for Yi ethnic group with HIV/AIDS.Methods: Cross-sectional study was carried out on the adult patients with AIDS of Yi ethnic group who received an antiviral treatment containing 400mg/d or600mg/d of efavirenz in a certain place in Sichuan Province.The clinical information of the patients was collected.The plasma concentration of efavirenz of patients was determined by ultra performance liquid chromatography,and the whole gene sequence of the CYP2B6 on the patients was performed.To compare the plasma concentration of patients with different doses of efavirenz,and to explore the relationship between body weight,age,sex,CYP2B6 single nucleotide polymorphism and the plasma concentration of efavirenz.SPSS 22.0 and Haploview 4.1 were used for data analysis.Results: A total of 122 Yi ethnic group with HIV/AIDS were included(94 patients take efavirenz at dose of 600mg/d,28 patients take efavirenz at dose of 400mg/d).The plasma concentration of all patients in the 600mg/d group and 400mg/d group were more than 1000ng/ml,22.3% of patients with plasma concentration of efavirenz in600mg/d group was more than 4000ng/ml,while 42.9% of patients with plasma concentration in 400mg/d group was more than 4000ng/ml.The median plasma concentration of efavirenz in 400mg/d group was higher than that in 600mg/d group(P=0.001).In the 400mg/d group,it was found that the plasma concentration of people with body weight<50kg was higher than that of people with body weight ≥ 50kg(P=0.011).However,there was no significant difference in the plasma concentration of efavirenz in patients of different ages and sexes(P>0.05).192 single nucleotide polymorphisms were found in the CYP2B6 coding region of all patients.The single nucleotide polymorphisms related to the high plasma concentration of efavirenz were analyzed in this study,the result suggest that 516G>T,785A>G,823-197T>C,1294+53C>T,171+4335T>C and 171+967C>A were associated with the high plasma concentration of efavirenz(>4000ng/ml)(P<0.05),while 485-18C>T were not associated with it(P=0.717).After H-W test,MAF>0.05 and Tag SNP substitution,all SNPs detected in the coding region of patients in the 600mg/d group obtained eight relatively independent single nucleotide polymorphisms that were representative and related to the high plasma concentration of efavirenz,namely 516G>T,171+4335T>C,823-197T>C,171+967C>A,171+5876T>C,172-5390T>C,785A>G and 645+727G>T.Among them,171+5876T>C heterozygous mutation predicted more than 50% of the high plasma concentration of efavirenz.Among homozygous mutations,516G>T,172-5390T>C,171+4335T>C had a predictive value of more than 50% for the high plasma concentration of efavirenz.Conclusion: The results approve the feasibility of reducing EFV in the Yi ethnic group,and suggest that body weight may be related to plasma concentration of efavirenz.In addition,eight relatively independent CYP2B6 single nucleotide polymorphisms associated with the high plasma concentration of efavirenz were identified.And this paper suggest that the antiviral regimen of Yi ethnic group with HIV/AIDS can be further optimized based on weight and CYP2B6 single nucleotide polymorphism. |
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