Data regarding the effect of the
CYP2B6 18492T→C polymorphism on plasma
efavirenz concentrations and 96-week virologic responses in patients coinfected with HIV and
tuberculosis (TB) are still unavailable. A total of 139 antiretroviral-naive HIV-infected adults with active TB were prospectively enrolled to receive
efavirenz 600 mg-
tenofovir 300 mg-
lamivudine 300 mg. Eight single nucleotide polymorphisms (SNPs) within
CYP2B6 were genotyped. Seven SNPs, including 64C→T, 499C→G, 516G→T, 785A→G, 1375A→G, 1459C→T, and 21563C→T, were included for
CYP2B6 haplotype determination. The
CYP2B6 18492T→C polymorphism was studied in 48 patients who carried haplotype *1/*1. At 12 and 24 weeks after antiretroviral
therapy, plasma
efavirenz concentrations at 12 h after dosing were measured. Plasma HIV
RNA was monitored every 12 weeks for 96 weeks. Of 48 patients {
body weight [mean±standard deviation (SD)], 56±10 kg}, 77% received a
rifampin-containing anti-TB regimen. No drug resistance-associated mutation was detected at baseline. The frequencies of the wild type (18492TT) and the heterozygous (18492TC) and homozygous (18492CC) mutants of the
CYP2B6 18492T→C polymorphism were 39%, 42%, and 19%, respectively. At 12 weeks, mean (±SD)
efavirenz concentrations of patients who carried the 18492TT, 18492TC, and 18492CC mutants were 2.8±1.6, 1.7±0.9, and 1.4±0.5 mg/liter, respectively (P=0.005). At 24 weeks, the
efavirenz concentrations of the corresponding groups were 2.4±0.8, 1.7±0.8, and 1.2±0.4 mg/liter, respectively (P=0.003). A low
efavirenz concentration was independently associated with 18492T→C (β=-0.937, P=0.004) and high
body weight (β=-0.032, P=0.046). At 96 weeks, 19%, 17%, and 28% of patients carrying the 18492TT, 18492TC, and 18492CC mutants, respectively, had plasma HIV
RNA levels of >40 copies/ml and developed
efavirenz-associated mutations (P=0.254). In summary, the
CYP2B6 18492T→C polymorphism compromises
efavirenz concentrations in patients who carry
CYP2B6 haplotype *1/*1 and are coinfected with HIV and
tuberculosis.