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Abstract
Although the reduction in HIV-1-related deaths with highly active antiretroviral therapy
(HAART) is similar in adults and children, the extent of the changes in two important
surrogate markers HIV-1 RNA levels and CD4+ T cell counts, differs widely. In most
paediatric studies virological response rates to HAART are inferior to those in adults.
This review provides an overview of the paediatric clinical studies using HAART and
seeks to improve the understanding of factors that may contribute to success or failure
of HAART in children. An overview of all current articles on paediatric clinical trials
using HAART is provided. 23 papers were available. HIV-1 RNA loads and CD4+ T cell
counts were used as primary outcome measures. Virological response rates were highly
variable, both among the different antiretroviral drugs but also among different studies
using the same medication. Four studies in which dosages of the administrated protease
inhibitor (PI) were adjusted after pharmacokinetic evaluation had superior virological
response rates compared with those in which fixed dosages were used. Immunological
response rates were more uniform than virological responses. In almost all studies
increases of CD4+ T cell counts are reported independent of the extent of the virological
response. Side-effects of HAART were generally mild, transient, and of gastrointestinal
origin. Significant percentages of patients with serum lipid abnormalities were reported
in three paediatric studies. However, signs of clinical lipodystrophy were not observed.
The inferior virological response rates, which have been reported in HIV-1 infected
children treated with HAART form a reflection of the challenges that are encountered
in the treatment of these children. Difficulties with adherence and with the pharmacokinetics
of PIs in children require an intensive, child-adjusted approach. A practical approach
to therapy in institutions without tertiary care facilities may be induction therapy
with a lopinavir containing regimen (lacking a need for therapeutic drug monitoring),
to reduce high viral load levels followed by an easily tolerated maintenance regimen,
for example containing abacavir or nevirapine.