Dose recommendations for lamivudine or emtricitabine in children with HIV and chronic kidney disease (CKD) are absent or not supported by clinical data. Physiologically based pharmacokinetic (PBPK) models have the potential to facilitate dose selection for these drugs in this population. Existing lamivudine and emtricitabine compound models in Simcyp®(v21) were verified in adult populations with and without CKD and in non-CKD paediatric populations. We developed paediatric CKD population models reflecting subjects with a reduced glomerular filtration and tubular secretion, based on extrapolation from adult CKD population models. These models were verified using ganciclovir as a surrogate compound. Then, lamivudine and emtricitabine dosing strategies were simulated in virtual paediatric CKD populations. The compound and paediatric CKD population models were verified successfully (prediction error within 0.5- to 2-fold). The mean AUC ratios in children (GFR-adjusted dose in CKD population/standard dose in population with normal kidney function) were 1.15 and 1.23 for lamivudine, and 1.20 and 1.30 for emtricitabine, with grade-3- and -4-stage CKD, respectively. With the developed paediatric CKD population PBPK models, GFR-adjusted lamivudine and emtricitabine dosages in children with CKD resulted in adequate drug exposure, supporting paediatric GFR-adjusted dosing. Clinical studies are needed to confirm these findings.