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) AUC_0-24hr was 2.64 (1.23 to 5.11) µg*h/mL and C_24h 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.