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Background:  Once-daily dosing may improve adherence to treatment of antiretroviral drugs. Lopinavir/ritonavir (LPV/r) has been developed as a twice-daily drug, however, the efficacy of a once-daily regimen in naïve patients is in debate. The aim of our study was to evaluate LPV/r peak and trough following once-daily administration in HIV-infected, naive children.

Methods:  We studied 28 children (17 females), weight median 24.9 kg (range 8.3 to 39.0), age median 9.25 (3.5 to 14 years), body mass index median 16.51 (7.68 to 21.64), 4 Hispanic, 5 black, and 19 Caucasian. They were treated with 230/57.5 mg/m² or 460/115 mg/m² LPV/r given twice daily or once daily, respectively. Two patients received LPV/r 300/75 mg/m² twice daily with efavirenz. Of the 28 children, 7 received the daily dose with a once-daily regimen. Median length of therapy with LPV/r at the time of blood sampling was 18.5 months (range 4 to 44). All patients were protease inhibitor-naïve. Median viral load at baseline was 121.500 copies/mL (3900 to 1,900,000) and CD4⁺ at baseline 450 cells/mm³ (4 to 1452). Blood samples were drawn at following times after a steady state dose of LPV/r: time 0, 1, 3, 4, and 6 hours. LPV/r plasma concentrations were determined with a HPLC assay.

Results:  C_min results were lower with the once-daily regimen than with the twice-daily regimen (p < 0.05, Mann-Whitney U test). The variability of pharmacokinetic parameters was extremely high. Analysis of the correlation between body mass index and pharmacokinetic parameters did not reveal any significant correlation (body mass index and C_max, p = 0.4043; body mass index and C_min p = 0.3919).

Conclusions:  Although we found a lower C_min of LPV/r with the once-dailydosing regimen, such concentrations may be sufficient to inhibit the replication of wild type virus in most of the children. Therefore, a clinical trial of once-daily LPV/r in children is warranted.

Keywords: children; lopinavir; pharmacokinetics