Tenofovir Pharmacokinetics when Administered According to Weight-band Dosing in 15-kg HIV+ Children Receiving Tenofovir/Lamivudine/Efavirenz Once Daily
L Aurpibul1, Tim Cressey*1,2,3, O Wittawatmongkol4, V Sirisanthana1, W Phongsamart4, T Sudjaritruk5, and K Chokephaibulkit4
1Res Inst for Hlth Sci, Chiang Mai Univ, Thailand; 2Chiang Mai Univ Faculty of Associated Med Sci, Thailand; 3Harvard Sch of Publ Hlth, Boston, MA, US; 4Siriraj Hosp Faculty of Med, Mahidol Univ, Bangkok, Thailand; and 5Chiang Mai Univ Faculty of Med, Thailand
Background: An affordable once-daily dosing drug, such as tenofovir (TDF), is favorable for HIV+ children and adolescents to help improve adherence and quality of life. Our objective was to evaluate the steady-state pharmacokinetics of TDF prescribed according to weight-band dosing in combination with lamivudine (3TC) and efavirenz (EFV) in HIV+ children.
Methods: This was a prospective, single-arm, open-label, multi-center study of HIV+ children receiving NNRTI-based regimens, without TDF. Children were aged between 3 and 18 years, weighing ≥15 kg, and virologically suppressed were enrolled. Their first-line ARV regimen was modified to a once-daily regimen of TDF+3TC+EFV. TDF was prescribed according to weight-band dosing with acceptable doses between 90% and 125% of the recommended dose (8 mg/kg for age <8 years, and 210 mg/m2 for age ≥8 years): 150 mg for 15 to <22 kg, 225 mg for 22 to <33 kg, and 300 mg for >33 kg once daily. Intensive 24-hour blood sampling for pharmacokinetics was performed after 4 weeks. TDF plasma concentrations were determined by HPLC and pharmacokinetic parameters by non-compartmental analysis. Clinical information was retrieved from medical records.
Results: We enrolled 40 HIV+ children: 17 (34%) were male, mean (±SD) age was 11.7 (3.5) years, and CD4 cell count was 853 (399) cells/mm3. Mean duration on HAART was 354 (155) weeks prior to enrollment. Overall, the median (range) AUC0-24hr was 2.64 (1.23 to 5.11) µg*h/mL and C24h was 0.05 (0.02 to 0.12) µg/mL. The 90% confidence interval for the geometric mean AUC was within ±20% of that reported in adults. Pharmacokinetic parameters for children above and below 12 years of age are shown below:
Conclusions: TDF prescribed according to weight-band dosing as a part of once-daily ARV regimen in children achieved plasma exposures comparable to HIV+ adults receiving 300 mg TDF. No significant difference in pharmacokinetic parameters was found between children above and below 12 years of age.