Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age
Authors
Chadwick, Ellen GouldRodman, John H.
Britto, Paula
Powell, Christine
Palumbo, Paul
Luzuriaga, Katherine
Hughes, Michael
Abrams, Elaine J.
Flynn, Patricia M.
Borkowsky, William
Yogev, Ram
UMass Chan Affiliations
Department of PediatricsDocument Type
Journal ArticlePublication Date
2005-09-01Keywords
Age FactorsAntiretroviral Therapy, Highly Active
Child, Preschool
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Follow-Up Studies
HIV Infections
HIV-1
Humans
Infant
Infant, Newborn
Lamivudine
Male
Maximum Tolerated Dose
Prospective Studies
Risk Assessment
Ritonavir
Severity of Illness Index
Single-Blind Method
Survival Rate
Treatment Outcome
Zidovudine
Immunology and Infectious Disease
Pediatrics
Metadata
Show full item recordAbstract
BACKGROUND: Few data are available regarding clinical outcomes or dosing requirements for the protease inhibitor ritonavir in human immunodeficiency virus (HIV)-infected children younger than under 24 months of age. METHODS: This prospective, multicenter phase I/II open label treatment trial used ritonavir, zidovudine and lamivudine to treat protease inhibitor-naive, HIV-infected infants between the ages of 4 weeks and 24 months. Two sequential dosing cohorts were treated with 350 or 450 mg/m(2) ritonavir every 12 hours; this report includes results of pharmacokinetics, safety, tolerability and efficacy through 104 weeks of follow-up of all subjects. RESULTS: Fifty HIV-infected children were treated. By week 16, 36 had achieved HIV-1 RNA /mL (72% intent-to-treat, 84% as-treated analysis); by week 104, 18 maintained durable viral suppression (36% intent-to-treat, 46% as-treated). Poor medication adherence by caregiver report contributed to virologic failure. Few subjects experienced treatment-limiting toxicity: emesis or ritonavir refusal in 6 (12%); and severe but reversible anemia or elevated serum hepatic transaminases in 1 (4%) each. Apparent oral clearance was higher and the median predose concentrations were substantially lower than those found in adults. Median z scores for weight and height for age/gender were below normal at baseline but improved by week 104. CONCLUSIONS: A combination regimen of ritonavir, zidovudine and lamivudine was generally safe and produced sustained viral suppression in more than one-third of infants who initiated therapy before 2 years of age. Improved palatability of liquid preparations of protease inhibitors, supporting infrastructure and behavioral approaches to improve medication adherence with antiretrovirals will likely be necessary to further improve efficacy.Source
Pediatr Infect Dis J. 2005 Sep;24(9):793-800. DOI 10.1097/01.inf.0000177281.93658.dfDOI
10.1097/01.inf.0000177281.93658.dfPermanent Link to this Item
http://hdl.handle.net/20.500.14038/43464PubMed ID
16148846Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1097/01.inf.0000177281.93658.df