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Epstein–Barr virus (EBV) is a well-known cause of different types of malignancies particularly Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s lymphomas, and non-Hodgkin’s lymphomas including primary central nervous system lymphoma (PCNSL). A higher tendency of malignant transformation associated with EBV has been noticed in immunocompromised patients, such as human immunodeficiency virus (HIV) infected patients. The rapid and effective immune reconstitution is crucial to prevent PCNSL in HIV-positive patients. We present a clinical case of a young patient diagnosed with HIV infection and medicated with antiretroviral therapy (ART) with poor immunological recovery. After two weeks, he developed ventriculoencephalitis, observed in the cranial magnetic resonance imaging (MRI), caused by cytomegalovirus (CMV) and EBV, both with high serum viral load, rapidly evolving to PCNSL. With this unusual clinical case, the authors want to draw attention to the importance of rapid immunological reconstitution in preventing the progression of EBV infection to PCNSL, as well as encouraging the confirmation of the usefulness of early combination of chemotherapy and antiviral therapy, in order to reach a more effective treatment of this herpesvirus infection and associated malignancies.

An Unusual Case of CMV/EBV Ventriculoencephalitis with Evolution to Primary Central Nervous System Lymphoma in HIV-Positive Patient