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

Ellen G. Chadwick*, Edmund V. Capparelli, Ram Yogev, Jorge A. Pinto, Brian Robbins, John H. Rodman, Jie Chen, Paul Palumbo, Leslie Serchuck, Elizabeth Smith, Michael Hughes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)249-255
Number of pages7
JournalAIDS
Volume22
Issue number2
DOIs
StatePublished - Jan 2008

Keywords

  • HIV-1-infected infants
  • Lopinavir/ritonavir
  • Pharmacokinetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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