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Gerlach, Undine Ariane (2004): Interruption of antiretroviral treatment in HIV-infected children. Dissertation, LMU München: Faculty of Medicine
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Abstract

This study deals with the effects of treatment withdrawal in HIV-infected children. In a retrospective survey 35 HIV-infected children who were under medical treatment in the Hôpital Necker-Enfants Malades in Paris, France, were observed concerning their discontinuation of antiretroviral therapy after months or years of receiving treatment. All children had acquired HIV infection through vertical transmission and received antiretroviral therapy for at least ten months before interrupting therapy for different reasons between 1996 and 2000 (insufficiency, toxicity, inconvenience). The study group consisted of 16 girls and 19 boys with an average age of 10.4 ± 4.9 years at the time treatment was stopped. The average time of observation after treatment interruption was 325 ± 294 days. Plasma HIV RNA was tested approximately every three months using an RNA polymerase chain reaction test. The CD4 cell count was regularly checked approximately at the same time as the viral load and measured by flow cytometry. To estimate the presence of major mutations in the HIV reverse transcrip-tase and protease genes, genotypic resistance was tested before treatment interruption, in the absence of antiretroviral treatment and in the case of a restart of therapy, when a new combination of efficient agents had to be defined. Based on the assumption that the course of HIV RNA viral load and CD4 cell count depended on certain factors, distinctions were made between the medical history of viral load and CD4 cell count, age, sex and reason for treatment interruption. The changes of CD4 cell count and viral loads were then analysed to calculate the percentage of lost CD4 cells and the increase of viral load per day of treatment interruption. By the time the study was finished in December 2000, 21 children were still without any further anti-retroviral therapy whereas 14 children had to restart therapy. Even though we noticed a viral rebound in all patients within the first few weeks of treatment interruption, there were different profiles of immunological reaction. Especially children, who had good immune responses before treatment interruption and who had stopped therapy at an early age (under 5 years) before running the risk of virological treatment failure, showed the best results. On the contrary, patients who had stopped therapy because of virological treatment failure had a greater loss of CD4 cells and showed an important increase of viral load in the time off therapy so that a prolonged treatment interruption was not advisable for them. But even though therapy had to be restarted for 14 patients, a general reduction of time on drug therapy could be achieved. Similar to adult studies, our data suggest, that a significant proportion of HIV-infected children can be safely taken off therapy for a prolonged period of time in order to reduce toxicity and costs.