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Methotrexate + zidovudine is a combination chemotherapy regimen investigated for the treatment of HIV-related primary central nervous system lymphoma (HIV-PCNSL). Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, thereby disrupting DNA synthesis and cell replication. Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) primarily used for HIV infection, but in this context, it is used at high doses alongside methotrexate as part of a neoadjuvant strategy followed by radiotherapy. This specific regimen was evaluated in a Phase II clinical trial sponsored by the Centro di Riferimento Oncologico - Aviano to improve outcomes in patients with HIV-associated CNS malignancies by utilizing the potential synergistic effects of these agents in the central nervous system.
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