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Background:  Lopinavir (LPV) is a protease inhibitor (PI) that is co-formulated with ritonavir (r). The pediatric approved dose is 230/57.5 mg/mē taken twice daily with food. In HIV-infected children a once-daily dosing schedule may offer an advantage to convenience and adherence. We studied the pharmacokinetics, tolerability, and efficacy of once-daily LPV/r in HIV-1-infected children.

Methods:  HIV-1-infected children on stable ART with a viral load < 50 copies/mL for at least 6 months received LPV/r 460/115 mg/mē (total daily dose of approved regimen) once daily with zidovudine and lamivudine. LPV/r was taken with food in the morning. Blood samples for LPV assay were collected at 0, 2, 4, 6, 8, 12, 18, and 24 hours after observed intake on day 14. Afterward, time of dosing could be changed to the evening. Plasma samples were collected at day 28 and months 2, 3, and 6 for LPV/r assay. Clinical assessment included plasma RNA levels, lymphocyte counts, biochemistry, hematology, and adverse events monitoring.

Results:  A total of 14 HIV-infected children, 7 boys and 7 girls, with a median age of 5.19 (range 1.42 to 12.85) years completed at least 6 months of follow-up. The chosen dosage of LPV/r , 460/115 mg/mē once daily, resulted in comparable LPV plasma levels to those in adults after a 800/200 mg once-daily regimen. In only 3 of the 14 patients C_trough was considered to be too low (< 1.0 mg/L) and thus an increase of dosage was necessary; 11 children chose to take LPV/r with their evening meal; and 44% (17 of 39) of the LPV/r plasma levels were higher than their corresponding values on day 14. 2 of 3 children taking LPV/r with breakfast had lower plasma levels than those on day 14. All 14 patients had HIV-1 RNA levels < 50 copies/mL after 6 months of treatment. CD4 cell counts did not change significantly during the study. This once-daily regimen of LPV/r was generally well tolerated. Of the 14 children, 6 suffered from transient mild gastrointestinal side effects. Cholesterol and triglyceride levels were stable during 6 months of follow-up.

Conclusions:  LPV/r 460/115 mg/mē once daily led to LPV plasma levels comparable to those in adults. In only 3 of 14 patients was dosage increase necessary because of low C_trough. Intake with a large meal (like dinner) is important to obtain adequate plasma levels when LPV/r is dosed once daily in children. No virologic failure occurred. Once-daily administration of LPV/r was well tolerated. Lipids remained stable.

Keywords: lopinavir/ritonavir; once-daily; children