Immunopathogenesis of HIV-associated dementia.
This review provides a subjective analysis of the advances in our understanding of the immunopathogenesis of HIV-associated dementia that have occurred over the past 12 months. The review will focus on the following areas: (i) the role of chemokines and cytokines; (ii) the role of astrocytes, astrocyte cell death and non-productive infection of astrocytes; (iii) a model of the neuropathogenesis of HIV-associated dementia and its impact on treatment paradigms and future research. The requirements for the development of HIV-associated dementia are immunosuppression, the loss of macrophage regulation, central nervous system HIV infection of microglia and macrophages with a neurovirulent HIV strain, restricted HIV infection of astrocytes, and astrocyte cell death, all of which lead to an intracellular milieu that is neurotoxic. This cascade can be prevented and probably reversed by the use of highly active antiretroviral therapy, which controls viral replication both systemically and centrally. However, for those patients who have resistant virus and persistently high levels of replication, or who develop resistance or toxicity, other treatment strategies need to be developed. The control of excessive microglial and macrophage activation or a diminution of astrocyte and neuronal apoptosis could have benefits in terms of cognitive function. We therefore need to develop further our understanding of the immunopathogenesis of HIV-associated dementia so that we can control a number of other steps in the cascade rather than simply controlling the viral replication.
Wesselingh
S L
SL
Infectious Diseases Unit, Alfred Hospital, Monash University, Prahran, Victoria, Australia. s.wesselingh@alfred.org.au
Thompson
K A
KA
D015526:AIDS Dementia Complex / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology / Q000821:virology; D016923:Cell Death / Q000276:immunology; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006678:HIV / Q000276:immunology; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D017628:Microglia / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000276:immunology
D018925:Chemokines; D016207:Cytokines