HIV-1 and the central nervous system.

Abstract

Fifteen years after the discovery of HIV-1-infected cells in cerebrospinal fluid (CSF) and brain parenchyma of HIV-1-infected persons, the priorities among the pathophysiological questions related to brain infection have changed and new ones have been raised. The relationship between the neuropathogenesis of HIV-1 infection and that of HIV-1 infection in general has become even closer. Indeed, the most important recent breakthrough has come from observations of the effects of highly active antiviral therapy (HAART). First, HAART has a beneficial effect on neurological symptoms in some but not all patients. Second, HAART allows 60% of patients to maintain plasma and CSF HIV-1 RNA levels under the detection threshold, but the demonstration of non-eradication of the virus in these patients has been repeatedly made. This has led to the rather indefinite concepts of HIV-1 “sanctuaries”, the brain being one of them, and of “reservoir cells”, microglia and astrocytes probably among them. It remains to be determined whether there is a persisting residual viral replication in glial cells even in patients under efficient HAART or if there is a bonafide viral latency, which can be induced toward active viral replication under certain circumstances. It is also important to determine whether the chronic infection in glial cells is deleterious to nearby neuronal networks.KeywordsHuman Immunodeficiency Virus TypeQuinolinic AcidHuman Brain Microvascular Endothelial CellActive Viral ReplicationGlial Cell ActivationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.