%0 Journal Article
%T Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults
%A Sumonmal Uttayamakul
%A Sirirat Likanonsakul
%A Weerawat Manosuthi
%A Nuanjun Wichukchinda
%A Thareerat Kalambaheti
%A Emi E Nakayama
%A Tatsuo Shioda
%A Srisin Khusmith
%J AIDS Research and Therapy
%D 2010
%I BioMed Central
%R 10.1186/1742-6405-7-8
%X 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 CYP2B6-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 ¡À 2.32, 13.62 ¡À 4.21 and 8.48 ¡À 1.30 mg/L, respectively) were significantly higher than those with GT (3.43 ¡À 0.29, 3.35 ¡À 0.27 and 3.21 ¡À 0.22 mg/L, respectively) (p < 0.0001) or GG genotypes (2.88 ¡À 0.33, 2.45 ¡À 0.26 and 2.08 ¡À 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 ¡À 9.49, 7.94 ¡À 2.76 and 9.44 ¡À 0.17 mg/L, respectively) tended to be higher than those carrying GT (5.65 ¡À 0.54, 5.58 ¡À 0.48 and 7.03 ¡À 0.64 mg/L, respectively) or GG genotypes (5.42 ¡À 0.48, 5.34 ¡À 0.50 and 6.43 ¡À 0.64 mg/L, respectively) (p = 0.003, p = 0.409 and p = 0.448, respectively). Compared with the effects of CYP2B6-516TT 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 CYP2B6-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 CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine concentrations when co-administered with rifampicin in HIV/TB co-infected Thai adults.CYP2B6-TT genotype had impact on plasma efavirenz and nevirapine concentrations, while rifampicin co-administration had only small effects.Tuberculosis (TB) is the most common opport
%U http://www.aidsrestherapy.com/content/7/1/8