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. SUBJECTS.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 ant...

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Published in:	The Pediatric infectious disease journal Vol. 22; no. 3; pp. 216 - 223
Main Authors:	SÁEZ-LLORENS, XAVIER, VIOLARI, AVYI, DEETZ, CARL O, RODE, RICHARD A, GOMEZ, PERRY, HANDELSMAN, EDWARD, PELTON, STEPHEN, RAMILO, OCTAVIO, CAHN, PEDRO, CHADWICK, ELLEN, ALLEN, UPTON, ARPADI, STEPHEN, CASTREJÓN, MARIA MERCEDES, HEUSER, RENEE S, KEMPF, DALE J, BERTZ, RICHARD J, HSU, ANN F, BERNSTEIN, BARRY, RENZ, CHERYL L, SUN, EUGENE
Format:	Journal Article
Language:	English
Published:	Baltimore, MD Lippincott Williams & Wilkins, Inc 01-03-2003 Philadelphia, PA Lippincott Hagerstown, MD
Subjects:	Administration, Oral Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Biological Availability Chemistry, Pharmaceutical Child Child, Preschool Confidence Intervals Dose-Response Relationship, Drug Drug Administration Schedule Drug Therapy, Combination Female Follow-Up Studies HIV Infections - diagnosis HIV Infections - drug therapy Human viral diseases Humans Infant Infectious diseases Lopinavir Male Maximum Tolerated Dose Medical sciences Multivariate Analysis Pharmacology. Drug treatments Pyrimidinones - administration & dosage Pyrimidinones - pharmacokinetics Reverse Transcriptase Inhibitors - administration & dosage Reverse Transcriptase Inhibitors - pharmacokinetics Ritonavir - administration & dosage Ritonavir - pharmacokinetics RNA, Viral - drug effects Severity of Illness Index Time Factors Treatment Outcome Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Viral Load Human Immunopathology Drug combination Ritonavir Treatment efficiency Lopinavir Enzyme inhibitor human immunodeficiency virus infection AIDS Immune deficiency Infection Chemotherapy Treatment Lopinavir/ritonavir children Viral disease Antiviral Child Protease inhibitor
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Summary:	BACKGROUND.Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. SUBJECTS.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 or 300/75 mg/m 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 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-treatmissing = 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; 10.3%) and ARV-experienced subjects (284 cells/mm; 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.
ISSN:	0891-3668 1532-0987
DOI:	10.1097/01.inf.0000055061.97567.34