Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children

Objectives: To obtain data on the pharmacokinetics of efavirenz in children in clinical practice. Methods: HIV-1-infected children received efavirenz capsules or tablets in accordance with manufac-turer’s dosing recommendations. Plasma was collected at regular visits and analysed by HPLC. The therapeutic range of efavirenz was defined as 1.0–4.0 mg/L. Results: Thirty-three children were included. Median (range) age, body weight, dose and dose/kg were 8.2 (2.1–16.7) years, 24 (12–62) kg, 300 (200–800) mg and 13.3 (9.7–22.5) mg/kg, respectively. Median (range) efavirenz plasma concentration at first sampling was 2.8 (0.13–11.6) mg/L. Plasma concen-trations were not dependent on age (P 5 0.97) or dose/kg (P 5 0.87). A total of 307 efavirenz plasma concentrations were determined. Forty-five samples (14.7%) contained>4.0 mg/L, and 27 samples (8.8%) contained <1.0 mg/L. Eight children (24%) reported persistent adverse events probably caused by efavirenz [concentration problems (5), sleep disorder (1), psychotic reaction (1) and seizure (1)]; six discontinued efavirenz for this reason. A non-significant trend existed towards a higher proportion of toxic efavirenz plasma concentrations (>4.0 mg/L) in subjects who reported efavirenz adverse events: 25.9 % versus 12.8 % (P 5 0.23; t-test). Viral load was <50 copies/mL in all 27 subjects who continued efavirenz, despite occasional subtherapeutic efavirenz plasma concentrations in 12 children. Th