Neuropathology and neurodegeneration in human immunodeficiency virus infection - Pathogenesis of HIV-induced lesions of the brain, correlations with HIV-associated disorders and modifications according to treatments

A variety of HIV-induced lesions of the central nervous system (CNS) have b een described, including HIV encephalitis, HIV leukoencephalopathy, axonal damage, and diffuse poliodystrophy with neuronal loss of variable severity resulting, at least partly, from an apoptotic process. However, no correlat ion could be established between these changes and HIV dementia (HIVD). Fro m our study of HIV infected patients, it appeared that neuronal apoptosis i s probably not related to a single cause. Microglial and glial activation, directly or indirectly related to HIV infection, plays a major role in neur onal apoptosis possibly through the mediation of oxidative stress. In our p atients with full-blown AIDS, this mechanism predominated in the basal gang lia and correlated well with HIVD. Axonal damage, either secondary to micro glial activation, or to systemic factors also contributes to neuronal apopt osis. Although massive neuronal loss may be responsible for HIVD in occasio nal cases, we conclude that neuronal apoptosis is a late event and does not represent the main pathological substrate of HIVD. The dementia more likel y reflects a specific neuronal dysfunction resulting from the combined effe cts of several mechanisms, some of which may be reversible. Introduction of highly active antiretroviral therapy dramatically improved patient surviva l. however, its impact on the incidence and course of HIVD remains debatabl e. In our series, the incidence of HIVE has dramatically decreased since th e introduction of multitherapies, but a number of cases remain whose cognit ive disorders persist, despite HAART. The poor CNS penetration of many anti retroviral agents is a possible explanation, but irreversible "burnt out" H IV-induced CNS changes may also be responsible.