A prospective explorative cross sectional clinical study to investigate the neurocognitive effects of human Immunodeficiency virus and the influence of highly active anti retroviral (HAART) therapy on CSF viral replication and biomarkers for neurodegeneration in HIV infected patients on chronic therapy with HAART

Treatment with ART leads to partial recovery of immunity and delay of disease
progression in the majority of HIV infected patients. However there are
concerns that, despite effective suppression in peripheral blood, HIV
replication continues in sanctuary sites. The central nervous system is one of
the important sanctuary sites for HIV, and therefor HIV may have many
neurological manifestations. Persistent viral replication in the CNS and
continuous exposure to viral protein may induce cerebral damage at long term.
Limited penetration of antiretroviral drugs into the CNS is considered one of
the main reasons for persistent viral replication. In this study it will be
investigated whether the different HAART regimes used in the UMC St Radboud
suppress HIVRNA replication in CSF effectively. Secondary objectives of this
study are to investigate the development of HIV resistance in the CSF, whether
sufficient (above IC50) drug levels in the CSF can be reached and whether
neurocognitive impairment and changes in CSF biomarkers for neurodegeneration
appear during treatment.

1 To investigate the influence of HAART on CSF viral load, development of HIV
resistance, neurotransmitters and biomarkers for neurodegeneration
2 To explore the neurocognitive effects of HIV infection and its treatment
3 To investigate the relationship between CSF drug levels and neurocognitive
effects and CSF HIV RNA

In a group of 40 HIV seropositive patients on HAART therapy the following tests
will be done:

- CSF puncture for determination of HIVRNA, drug levels, proteins and
biomarkers for neurodegeneration
- neuropsychological tests
- MRI of the brain
.

pain and discomfort during and after the CSF puncture