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


CONCLUSIONS
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.
Chadwick
Ellen G
EG
Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA. egchadwick@childrensmemorial.org
Capparelli
Edmund V
EV
Yogev
Ram
R
Pinto
Jorge A
JA
Robbins
Brian
B
Rodman
John H
JH
Chen
Jie
J
Palumbo
Paul
P
Serchuck
Leslie
L
Smith
Elizabeth
E
Hughes
Michael
M
D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D007223:Infant; D061466:Lopinavir; D008297:Male; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir