Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 Week results

Academic Article

Abstract

  • OBJECTIVE: To investigate pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r)-based therapy in HIV-1-infected infants 6 weeks to 6 months of age. METHODS:: A prospective, multicenter, open-label trial of 21 infants with HIV-1 RNA > 10 000 copies/ml and treated with LPV/r 300/75 mg/m twice daily plus two nucleoside reverse transcriptase inhibitors. Intensive pharmacokinetic sampling was performed at 2 weeks and predose concentrations were collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4-12 weeks for 24 weeks. RESULTS: Median age at enrollment was 14.7 weeks (range, 6.9-25.7) and 19/21 completed ≥ 24 weeks of study. Although LPV/r apparent clearance was slightly higher than in older children, the median area under the concentration-time curve 0-12 h (67.5 μg.h/ml) was in the range reported from older children taking the recommended dose of 230/57.5 mg/m. Predose concentrations stabilized at a higher level after the first 2 weeks of study. In as-treated analysis at week 24, 10/19 (53%) had plasma HIV-1 RNA < 400 copies/ml (median change, -3.33 log10 copies/ml); poor adherence contributed to delayed viral suppression, which improved with longer follow-up. Three infants (14%) had transient adverse events of grade 3 or more that were possibly related to study treatment but did not require permanent treatment discontinuation. CONCLUSION: Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily dose of 300/75 mg/m LPV/r provided similar exposure to that in older children, was well tolerated and provided favorable virological and clinical efficacy. © 2008 Lippincott Williams & Wilkins, Inc.
  • Authors

    Published In

  • AIDS  Journal
  • Digital Object Identifier (doi)

    Author List

  • Chadwick EG; Capparelli EV; Yogev R; Pinto JA; Robbins B; Rodman JH; Chen J; Palumbo P; Serchuck L; Smith E
  • Start Page

  • 249
  • End Page

  • 255
  • Volume

  • 22
  • Issue

  • 2