Neuronal apoptosis in human immunodeficiency virus infection

Neuronal apoptosis has been shown to occur in HIV infection by a number of in vivo and in vitro studies, however, the cause of neuronal damage in AIDS is still unclear and its relationships with the cognitive disorders characteristic of HIV dementia remain a matter of debate. In this review, based on our experience, we analyse the techniques used to identify neuronal apoptosis on post-mortem AIDS brains and describe the relationships of neuronal apoptosis with the stage of disease, a history of HIV-dementia, the degree of productive HIV infection, microglial activation, blood-brain barrier involvement and axonal damage. We conclude that the severity of neuronal apoptosis in the cerebral cortex correlates with the presence of cerebral atrophy, but not with the cognitive disorders. There is no global quantitative correlation between neuronal apoptosis and HIV encephalitis, microglial activation or axonal damage. However we found some topographical correlation between these changes. We conclude that neuronal apoptosis and consequent neuronal loss, in HIV infected patients, are probably not related to a single cause. It seems likely that microglial activation, directly or indirectly related to HIV infection of the CNS, plays a major role in its causation possibly through the mediation of oxidative stress. Axonal damage, either secondary to microglial activation, or to the intervention of systemic factors may also contribute to neuronal apoptosis.