Abstract
BACKGROUND: Chimeric antigen receptor T-cell therapy has emerged as a highly effective treatment for relapsed and refractory lymphomas; however, its application in individuals with human immunodeficiency virus remains underexplored. People with human immunodeficiency virus face an increased risk of developing malignancies such as lymphoma, where standard chemotherapy often results in suboptimal responses and heightened toxicity. OBJECTIVE: To review and synthesize current literature on the use of chimeric antigen receptor T-cell therapy and bispecific antibodies in human immunodeficiency virus-associated lymphoma, examining efficacy, safety, and potential barriers to implementation. METHODS: A systematic review of the literature was conducted using PubMed. Included studies comprised clinical trials, cohort studies, case reports, and preclinical research published between January 2000 and September 2024. Search terms included "HIV," "lymphoma," "CAR T cell therapy," "bispecific antibodies," "immunotherapy," and "HIV-associated lymphoma." RESULTS: Preliminary data suggest chimeric antigen receptor T-cell therapy is feasible in human immunodeficiency virus-positive patients, with response rates comparable to human immunodeficiency virus-negative populations and manageable adverse events, including cytokine release syndrome and neurotoxicity. Engineering chimeric antigen receptor T cells to target human immunodeficiency virus-infected cells is under investigation as a potential curative strategy. However, challenges such as immunosuppression, low antigen expression, and interactions with antiretroviral therapy complicate treatment. Bispecific antibodies have shown promise in hematologic malignancies, but data in people with human immunodeficiency virus remain limited due to trial exclusions. CONCLUSION: Early findings support the feasibility and potential efficacy of chimeric antigen receptor T-cell therapy in human immunodeficiency virus-associated lymphoma. Larger, controlled trials are needed to establish safety, optimize treatment strategies, and expand therapeutic options for people with human immunodeficiency virus.