Neurological, visual and neurocognitive performance in pediatric HIV-1- infected patients as compared to healthy controls.

Before the era of combined antiretroviral therapy (cART), perinatally infected
HIV-positive children frequently presented with serious neurological
dysfunctioning (prevalence varying from 30%-50%), including HIV-encephalopathy,
as characterized by impaired brain growth and acquired microcephaly,
symmetrical motor deficits and loss of or failure to attain developmental
milestones. Early neuroimaging studies of HIV-encephalopathy using computed
tomography (CT) demonstrated cerebral atrophy, calcifications in the basal
ganglia and white matter changes2. Since HIV-infected children are being
treated with cART, the incidence of HIV-encephalopathy has decreased while in
the meantime neuro-imaging abnormalities shown by these conventional
neuroimaging techniques have improved. Children can present with other
neurologic disorders such as seizures, headaches and neurocognitive impairments
(e.g. learning-, behavioural-, and motor deficits). The etiology of this
neurocognitive impairment is complex and, most likely, not purely biologically
determined. Environmental factors, such as home environment and socioeconomic
status (SES), may play a confounding role in cognitive development. In our
patient group, the SES is generally lower than in the average population.
Comparative data on neurological and neurocognitive findings between
HIV-infected and healthy controls with equal SES and living within similar
environments are lacking.
Since neurological and neurocognitive disorders can not be diagnosed until they
are clinically obvious, the availability of objective, reliable, non-invasive
markers may offer great advantages in assessing early central nervous system
(CNS) involvement in HIV-positive children. Standardized neuropsychological
assessment (NPA) and several advanced neuroimaging tests as well as
ophthalmological measurements are available to study the neurological,
neurocognitive and ophthalmological disorders in HIV-positive children. In
addition, biochemical tests and measurement of cART concentration levels in
cerebrospinal fluid (CSF) and blood, and combining these results with the
earlier mentioned NPA, neuroimaging and ophthalmological tests, will provide
more insight in the pathophysiology of CNS involvement of HIV and its clinical
consequences.

To evaluate neurologic- and cognitive disorders, neuroimaging and
ophthalmological alterations in perinatally HIV-infected children in comparison
to matched (with respect to age, sex, race, home environment and socio-economic
status) healthy controls. To measure cART concentration levels in CSF and blood
and correlating the results with the outcome of the NPA, neuroimaging and
ophthalmological tests.

An observational cross-sectional case-control study in which all participants
will undergo neuropsychological tests (NPA), advanced MRI techniques (MRS, DTI,
ASL), and ophthalmological investigation (optical coherence tomography; OCT).
In addition, several clinical and laboratory factors will be measured.

This study is classified as an observational study in subjects incompetent to
give informed consent. HIV positive children will undergo NPA, MRI, LP and
venous blood sampling as part of their normal treatment plan. For this study,
they will undergo one additional MRI and LP, and one ophthalmological
examination. Any venous blood sampling will as much as possible be combined
with standard blood sampling.
Controls are previously unexposed to any of the examinations. All patients are
given extensive information on all tests and will be included on voluntary
basis.
During all procedures we will guarantee guidance from research staff for all
participants. Parents/guardians can join their child at all times except the
NPA, which will be taken by an experienced pediatric neuropsychologist will
guide the participant.
Our research question is group related. To understand the pathophysiology of
neurocognitive deficits still found in HIV positive children (in the era of
cART) we need to evaluate patients at an age as early as possible, without the
confounding factors of general aging. We need the control group to minimize
confounding effects of sex, age, race, home environment and socioeconomic
status.
By accomplishing this study, we may be able to diagnose neurological and
neurocognitive disorders at an early stage in HIV positive patients. The
patients may benefit from close monitoring, and in the future early
intervention could improve their general development.
Former case-controlled pediatric neuro-imaging studies have obtained medical
ethical approval and have produced satisfying results.