Background. The search for an aetiology of central nervous system (CNS) lesions In HIV patients can be extremely challenging. Aim. To establish the nature and character of CNS lesion according to the data of pathological examination of deceased HIV-patients who had an antemortem clinical diagnosis of unspecified encephalitis. Materials and methods. We analysed clinical and laboratory data of 225 HIV-patients admitted to the ICU at the Infectious Clinical Hospital №2 (Moscow, 2018). The principal diagnosis was unspecified encephalitis characterized by cerebral oedema. Had died 183 (67.9%) patients. We conducted pathological examination in 43 (23.5%). Results. CNS lesions occurred in 331 patients (58.8% of 563 ICU). The antemortem diagnosis established were as follows: 12.1% - toxoplasmosis; 6.6% - HIV-encephalitis; 5.1% - CNS lymphoma; 3.6% - cryptococcal meningoencephalitis; 3.0% - cytomegaloviral diseases; 2.1% - progressive multifocal leukoencephalopathy. The cause of the pathology remained unidentified in 225 patients (68% with CNS lesions). Majority of patients were ART-naive. Post-mortem verification was conducted in 29 (67.4%) deceased patients, of which HIV-encephalitis - 34.5%, toxoplasmosis - 10.3%, progressive multifocal leukoencephalopathy - 3.4%. The nature of brain damage in the remaining 20.7% cases was not established even after post-mortem investigation. Productive lepto-meningitis - 8 (27.6%), indicating a prolonged duration of the inflammatory process. In the brain 48.1% patients with subacute and productive changes, had a pre-hospital time of more than 30 days, in contrast to 11.1% of patients who had acute pathological processes in the CNS (p<0.05). Autopsy didn't reveal any inflammatory changes in the brain in 14 (32.6%) patients, though cerebral oedema - 93.3%, haemorrhagic syndrome - 60% cases. Conclusion. Accurate retrospective identification of the aetiology of CNS lesions combined with assessing in vivo characterisation of the pathological process plays an essential role in subsequent formation of diagnostic approaches in pathologies of the CNS in HIV-patients. © 2021 Consilium Medikum. All rights reserved.