NEUROPATHOLOGY OF EARLY HIV-1 INFECTION

Early HIV-1 invasion of the central nervous system has been demonstrat ed by many cerebrospinal fluid studies; however, most HIV-1 carriers r emain neurologically unimpaired during the so called ''asymptomatic'' period lasting from seroconversion to symptomatic AIDS. Therefore, neu ropathological studies in the early pre-AIDS stages are very few, and the natural history of central nervous system changes in HIV-1 infecti on remains poorly understood. Examination of brains of asymptomatic HI V-1 positive individuals who died accidentally and of rare cases with acute fatal encephalopathy revealing HIV infection, and comparison wit h experimental simian immunodeficiency virus and feline immunodeficien cy virus infections suggest that, invasion of the CNS by HIV-1 occurs at the time of primary infection and induces an immunological process in the central nervous system. This includes an inflammatory T-cell re action with vasculitis and leptomeningitis, and immune activation of b rain parenchyma with increased number of microglial cells, upregulatio n of major histocompatibility complex class II antigens and local prod uction of cytokines. Myelin pallor and gliosis of the white matter are usually found and are likely to be the consequence of opening of the blood brain barrier due to vasculitis; direct damage to oligodendrocyt es by cytokines may also interfere. These white matter changes may exp lain, at least partly, the early cerebral atrophy observed, by magneti c resonance imaging, in asymptomatic HIV-1 carriers. In contrast, cort ical damage seems to be a late event in the course of HIV-1 infection. There is no significant neuronal loss at the early stages of the dise ase, no accompanying increase in glial fibrillary acid protein stainin g in the cortex, and only exceptional neuronal apoptosis. Although HIV -1 proviral DNA may be demonstrated in a number of brains, viral repli cation remains very low during the asymptomatic stage of HIV-1 infecti on. This makes it likely that, although opening of the blood brain bar rier may facilitate viral entry into the brain, specific immune respon ses including both neutralising antibodies and cytotoxic T-lymphocytes , continuously inhibits viral replication at that stage.