P1058 was an intensive pharmacokinetic study of LPV/RTV 300 mg/m2 b.i.d. in combination with EFV 350 mg/m2 q.d. in HIV-infected children receiving a NRTI-based regimen. The GM (90% CI) for both LPV and EFV AUC were within the target range for all the 15 patients enrolled. In contrast, although the LPV Cmin (GM 90% CI) contained values above the target upper limit of 7 mg/L, the EFV EstC24 hours GM (90% CI) contained values below the target lower limit of 0.9 mg/L.
, and AUC12
observed in our patients in the presence of EFV were 20%, 54%, and 10% higher, respectively, than those observed in adults receiving LPV/RTV 533/133 mg b.i.d. and EFV 600 mg q.d.7
Yet, our results were similar to those observed in HIV-infected children receiving LPV/RTV 300 mg/m2
b.i.d. in combination with EFV 14 mg/kg once daily.8
Of interest, 5 patients (33%) in this study had significantly lower LPV exposure, which is different from our findings where only 1 patient (6.6%) had LPV exposure below the target range of 0.9 mg/L. In the current study, patients received an EFV dose of 350 mg/m2
, which approximates 11 mg/kg; the recommended dose is 15 mg/kg. The lower EFV dose in our study may have had a smaller inhibitory effect on LPV metabolism resulting in a smaller number of patients with low LPV exposure. Furthermore, 5 patients in our study had LPV Cmin
above the target range of 7 mg/L. Each patient received LPV 400 mg, which was below the recommended 300 mg/m2
dose for 3 patients and approximately 35% higher in 2 patients. Again, higher LPV exposure in these patients is likely the result of the decreased inhibitory effect of the lower EFV dose.
The EFV Cmin
and AUC in our patients were 60% and 30% lower, respectively, compared with pediatric and adult patients.9
This difference is also likely due to the lower mg/kg equivalent EFV dose used in our study. However, an evaluation of EFV exposure in 15 South African children receiving a median dose of 352 mg/m2
, which was equivalent to 14 mg/kg, revealed that 40% of patients had an estimated Cmin
Another study evaluating EFV exposure in children dosed according to body weight-adjusted dose recommendations observed that 64% of patients had plasma concentrations below the targeted range.11
Taken together, these data suggest that the current weight-based dosing recommendations and the BSA-based dosing of 350 mg/m2
will often result in insufficient EFV exposure.
In conclusion, data from our study support the current strategy of increasing the LPV/RTV dose to 300 mg/m2 in the presence of EFV. However, EFV dosed at 350 mg/m2 may not be adequate in HIV-infected children. This conclusion is supported by several other studies evaluating EFV exposure in HIV-infected children, which also found plasma concentrations lower than expected relative to adult exposures, even when the recommended weight-based dosing was used. Because suboptimal EFV plasma concentrations can increase the development of viral resistance, additional studies are needed to further evaluate BSA-based and the current weight-based dosing of EFV.