Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.
BACKGROUND
Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult.


METHODS
The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children.


METHODS
One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/m(2) or 300/75 mg/m(2) lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated.


RESULTS
All subjects were escalated to the 300/75 mg/m(2) twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/ml at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/mm(3); 10.3%) and ARV-experienced subjects (284 cells/mm(3); 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event.


CONCLUSIONS
The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.
Sáez-Llorens
Xavier
X
Hospital del Niño, Panama City, Panama. xsaezll@cwpanama.net
Violari
Avyi
A
Deetz
Carl O
CO
Rode
Richard A
RA
Gomez
Perry
P
Handelsman
Edward
E
Pelton
Stephen
S
Ramilo
Octavio
O
Cahn
Pedro
P
Chadwick
Ellen
E
Allen
Upton
U
Arpadi
Stephen
S
Castrejón
Maria Mercedes
MM
Heuser
Renee S
RS
Kempf
Dale J
DJ
Bertz
Richard J
RJ
Hsu
Ann F
AF
Bernstein
Barry
B
Renz
Cheryl L
CL
Sun
Eugene
E
D000284:Administration, Oral; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D061466:Lopinavir; D008297:Male; D020714:Maximum Tolerated Dose; D015999:Multivariate Analysis; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012367:RNA, Viral / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019438:Ritonavir