Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age
Department of Pediatrics
Medical Subject Headings
Age Factors; Antiretroviral 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
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.
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Citation: Pediatr Infect Dis J. 2005 Sep;24(9):793-800. DOI 10.1097/01.inf.0000177281.93658.df