Interruption of antiretroviral treatment in HIV-infected children

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.