Therapeutic drug monitoring and pharmacogenetic, study of HIV-infected ethnic chinese receiving efavirenz-containing antiretroviral therapy with or without rifampicin-based anti-tuberculous therapy
Journal
PLoS ONE
Journal Volume
9
Journal Issue
2
Pages
e88497
Date Issued
2014
Author(s)
Lee K.-Y.
Tsai M.-S.
Wu B.-R.
Tang S.-Y.
Liu W.-C.
Abstract
Objectives: Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese. Methods: HIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively. Results: From October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33-0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97-9.59) in multivariate analysis. Conclusions: Despite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations. ? 2014 Lee et al.
SDGs
Other Subjects
efavirenz; rifampicin; adult; aged; article; Chinese; controlled study; drug blood level; drug monitoring; drug use; ethnicity; female; genotype; high performance liquid chromatography; highly active antiretroviral therapy; human; human cell; Human immunodeficiency virus infected patient; Human immunodeficiency virus infection; major clinical study; male; pharmacogenetics; polymerase chain reaction; restriction fragment length polymorphism; single nucleotide polymorphism; tuberculosis; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Antitubercular Agents; Aryl Hydrocarbon Hydroxylases; Asian Continental Ancestry Group; Benzoxazines; Body Weight; China; Drug Monitoring; Drug Therapy, Combination; Ethnic Groups; Female; HIV Infections; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide; Rifampin; Tuberculosis; Young Adult
Type
journal article