10.1186/1742-6405-7-8

Effects of <it>CYP2B6 </it>G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults

Abstract

<p>Abstract</p> <p>Background</p> <p>Cytochrome P450 2B6 <it>(CYP2B6) </it>metabolizes efavirenz and nevirapine, the major core antiretroviral drugs for HIV in Thailand. Rifampicin, a critical component of tuberculosis (TB) therapy is a potent inducer of CYP enzyme activity. Polymorphisms of <it>CYP2B6 </it>and <it>CYP3A4 </it>are associated with altered activity of hepatic enzyme in the liver and pharmacokinetics resulting in treatment efficacy. This study aimed to investigate whether <it>CYP2B6 </it>or <it>CYP3A4 </it>polymorphisms had effects on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.</p> <p>Results</p> <p>We studied 124 rifampicin recipients with concurrent HIV-1/TB coinfection, receiving efavirenz (600 mg/day) (n = 65) or nevirapine (400 mg/day) (n = 59) based antiretroviral therapy (ART). The frequencies of GG, GT and TT genotypes of <it>CYP2B6</it>-G516T were 38.46%, 47.69% and 13.85% in efavirenz group and 44.07%, 52.54% and 3.39% in nevirapine group, respectively. The mean 12-hour post-dose plasma efavirenz concentration in patients with TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation (10.97 ± 2.32, 13.62 ± 4.21 and 8.48 ± 1.30 mg/L, respectively) were significantly higher than those with GT (3.43 ± 0.29, 3.35 ± 0.27 and 3.21 ± 0.22 mg/L, respectively) (p < 0.0001) or GG genotypes (2.88 ± 0.33, 2.45 ± 0.26 and 2.08 ± 0.16 mg/L, respectively) (p < 0.0001). Likewise, the mean 12-hour post-dose plasma nevirapine concentration in patients carrying TT genotype at weeks 6 and 12 of ART and 1 month after rifampicin discontinuation (14.09 ± 9.49, 7.94 ± 2.76 and 9.44 ± 0.17 mg/L, respectively) tended to be higher than those carrying GT (5.65 ± 0.54, 5.58 ± 0.48 and 7.03 ± 0.64 mg/L, respectively) or GG genotypes (5.42 ± 0.48, 5.34 ± 0.50 and 6.43 ± 0.64 mg/L, respectively) (p = 0.003, p = 0.409 and p = 0.448, respectively). Compared with the effects of <it>CYP2B6-</it>516TT genotype, we could observe only small effects of rifampicin on plasma efavirenz and nevirapine levels. After 12 weeks of both drug regimens, there was a trend towards higher percentage of patients with <it>CYP2B6</it>-TT genotype who achieved HIV-1 RNA levels <50 copies/mL compared to those with GT or GG genotypes. This is the first report to demonstrate the effects of <it>CYP2B6 </it>G516T polymorphisms on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.</p> <p>Conclusions</p> <p><it>CYP2B6</it>-TT genotype had impact on plasma efavirenz and nevirapine concentrations, while rifampicin co-administration had only small effects.</p

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This paper was published in Directory of Open Access Journals.

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