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Randomized study of two doses of didanosine in children infected with human immunodeficiency virus
S Blanche1, T Calvez, C Rouzioux
1Unité d'Immunologie et d'Hématologie pédiatrique, INSERM U132, Hôpital Necker Enfants Malades, France.
Insights
This study evaluated two didanosine dosages in children with HIV, finding viral load reductions but no significant differences between doses. Potential liver toxicity was noted, especially in children with pre-existing liver conditions.
Area of Science:
- Pediatric infectious diseases
- Antiviral drug research
- Clinical pharmacology
Background:
- Limited data exist on didanosine (2'3'-Dideoxyinosine) efficacy and safety in pediatric HIV treatment.
- Zidovudine resistance or intolerance is common in children, necessitating alternative therapies.
Purpose of the Study:
- To compare two dosages of didanosine (120 vs 270 mg/m2 per day) in HIV-infected children.
- To assess the biologic effects and tolerability of didanosine in this population.
Main Methods:
- A single-center, randomized, open-label trial involving 34 HIV-infected children.
- Administration of didanosine for at least 6 months with serum level monitoring.
- Evaluation of viral markers (p24 antigenemia, viremia) and CD4+ cell counts.
Main Results:
- Significant reductions in HIV-p24 antigenemia and viremia were observed over time in both groups.
- Higher baseline CD4+ cell counts correlated with a more intense biologic response.
- No pancreatic or neurologic toxicities were reported; however, five children developed liver function abnormalities, with one fatality suggesting potential hepatotoxicity.
Conclusions:
- Didanosine demonstrated antiviral activity in children, but no significant differences were found between the two dosages tested.
- Potential hepatotoxicity requires careful monitoring, particularly in children with pre-existing liver disease.
- Further research is needed to establish optimal dosing and long-term safety profiles.
Abstract:
2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability.