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Virological failure in the central nerve system in HIV-infection


Virological failure in the central nerve system (CNS) during HAART: Characterization of HIV-surface protein (gp-120 V3 loop) of HIV-1-variants in peripheral blood and cerebrospinal fluid

In patients with HIV-encephalopathy there is a large amount of virus in the brain and the cerebrospinal fluid. The replication of virus in the brain is independent of the blood. In HIV-infected individuals there is a large number of virus variants at a given time-point. It is assumed that in the brain special virus variants with a specialized tropism for brain tissue exist.

In own experiments at the Department of Neurology at the University of Hamburg-Eppendorf, we could show that antiretroviral therapy in patients without HIV-encephalopathy led to a rapid reduction of HIV-load in cerebrospinal fluid. In contrast, patients with HIV-encephalopathy showed a similar reduction in blood, but an insufficient diminution of virus or even an increase of viral load in cerebrospinal fluid. This divergent response may cause a clinical failure and fosters the development of viral variants resistant to antiretroviral therapy.

The goal of the sponsored project is the analysis of the HIV-surface glycoprotein-120 with regard to any differences between blood and brain. Therefore, the viral gene for the gp-120 should be analyzed with regard to the use of alternative surface receptors (e.g. co-receptors) for infection of brain cells (neurons). The expected results may lead to the development of drugs that inhibit the infection of these target neurons.

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