Effect of rifampin/isoniazid-containing antituberculosis therapy on efavirenz pharmacokinetics in HIV-infected children aged 3 to 14 years old [Clinical Therapeutics]

We compared efavirenz pharmacokinetic (PK) parameters in children with TB/HIV coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children aged 3 to 14 years old with HIV infection with and without TB were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization recommended antituberculosis drugs dosages were used in the co-infected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated LC/MS/MS assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon Rank-sum test and within group by Signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age-Z-score and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz C_max, C_12h, C_min and AUC_0-24h were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C_12h, C_min and AUC_0-24h were lower in TB/HIV co-infected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC_0-24h was higher on than off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children.

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