Abstract
ObjectivesPlasma 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.MethodsHIV-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.ResultsFrom 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.ConclusionsDespite 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.
Highlights
Efavirenz is a potent non-nucleoside reverse-transcriptase inhibitor (NNRTI) and its combination with tenofovir and emtricitabine remains one of the preferred antiretroviral regimens for antiretroviral-naive patients without resistance-associated mutations to NNRTIs [1]
The wide inter-patient variability of efavirenz concentrations has been reported, which may be related to sex, weight, ethnicity, drug-drug interactions, and single-nucleotide polymorphism (SNP) of CYP2B6 [3,4,5,6,7,8]
We aimed to investigate the effect of concurrent use of rifampicin and CYP2B6 G516T polymorphisms on the plasma efavirenz concentrations in HIV-infected Taiwanese patients
Summary
Efavirenz is a potent non-nucleoside reverse-transcriptase inhibitor (NNRTI) and its combination with tenofovir and emtricitabine remains one of the preferred antiretroviral regimens for antiretroviral-naive patients without resistance-associated mutations to NNRTIs [1]. The recommended therapeutic levels of efavirenz at 12 hours are 1 to 4 mg/L [2]. Efavirenz is metabolized primarily through hepatic cytochrome P450 (CYP) 2B6. The wide inter-patient variability of efavirenz concentrations has been reported, which may be related to sex, weight, ethnicity, drug-drug interactions, and single-nucleotide polymorphism (SNP) of CYP2B6 [3,4,5,6,7,8]. Conflicting data regarding the aforementioned factors makes dose adjustment while co-administration with other drugs or weight-based adjustment problematic [9,10]
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