Ritonavir-Based Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus Type 1-Infected Infants Younger Than 24 Months of Age

Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 10/2005; 24(9):793-800. DOI: 10.1097/01.inf.0000177281.93658.df
Source: PubMed


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.
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.
Fifty HIV-infected children were treated. By week 16, 36 had achieved HIV-1 RNA <400 copies/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.
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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    • "The Children with HIV Early ART (CHER) trial in South Africa recently demonstrated a 76% reduction in morbidity, a 75% reduction in mortality, and notable short-term cost reductions when HIV-infected infants initiated ART before 3 months of age and before clinical signs and symptoms of HIV developed [33,34]. Based on this trial and a growing body of observational data [35-37], WHO pediatric treatment guidelines now recommend ART initiation for all HIV-infected infants under 24 months of age [6,32]. In order to facilitate ART initiation as soon as possible after infection, WHO recommends HIV diagnostic testing for all HIV-exposed infants (infants born to HIV-infected mothers) at 4-6 weeks of age [32]. "
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