Effect of Rifampicin on Efavirenz Pharmacokinetics in HIV-Infected Children With Tuberculosis

Setting: Rifampicin may reduce plasma efavirenz concentrations by inducing the expression of the cytochrome P450 2B6, which metabolizes efavirenz. However, there is no data in pediatric patient populations. Methods: We measured plasma efavirenz concentrations in 15 children during and after rifampicin-based antitubercular treatment. They were receiving standard closes of efavirenz as part of antiretroviral treatment. Trough concentration (C-min) was estimated by extrapolation of the log-linear concentration-time line to 24 hours after the previous dose. Results: Wide interpatient variation and marked bimodality of efavirenz concentrations were observed. Efavirenz C-min was not significantly different during vs. after antitubercular treatment (median 0.83 mg/L interquartile range 0.59-6.57 vs. median 0.86 mg/L interquartile range 0.61-3.56; P = 0.125). Nine (60%) and 8 (53%) children had subtherapeutic C-min (<1 mg/L) during and after antitubercular treatment, respectively. Conclusions: Concomitant rifampicin-based antitubercular treatment was not an important determinant of efavirenz concentrations. The substantial proportion of participants with estimated C-min <1 mg/L could result in the rapid emergence of efavirenz-resistant mutations and treatment failure.