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

Chadwick, Ellen Ga; Capparelli, Edmund Vb; Yogev, Rama; Pinto, Jorge Ah; Robbins, Brianc; Rodman, John Hc; Chen, Jied; Palumbo, Paule; Serchuck, Leslief; Smith, Elizabethg; Hughes, Michaeld; for the P1030 team

doi: 10.1097/QAD.0b013e3282f2be1d
Clinical Science

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/m2 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/m2. 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/m2 LPV/r provided similar exposure to that in older children, was well tolerated and provided favorable virological and clinical efficacy.

From the aDepartment of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA

bPediatric Pharmacology Research Unit, University of California, San Diego, California, USA

cSt. Jude Children's Research Hospital, Memphis, Tennessee, USA

dStatistical & Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, USA

eDivision of Infectious Diseases and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA

fDivision of Pediatric, Adolescent, and Maternal AIDS, USA

gDivision of AIDS, National Institutes of Health, Bethesda, Maryland, USA

hEscola de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Received 22 March, 2007

Revised 18 June, 2007

Accepted 28 September, 2007

Correspondence to Dr E.G. Chadwick, Division of Infectious Diseases, 2300 Children's Plaza, Box 20, Chicago, IL 60614, USA. E-mail: egchadwick@childrensmemorial.org

© 2008 Lippincott Williams & Wilkins, Inc.