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The persistence of HIV reservoirs and their spatial association with lymphoma highlights the need to clarify their role in lymphomagenesis. HIV reservoirs, which are established early during infection and maintained through clonal expansion, epigenetic silencing, and immune evasion, may contribute to lymphomagenesis through four interconnected mechanisms: provirus integration effects, viral protein-mediated disturbances, microenvironment dysregulation, and reservoir reactivation. Current therapeutic approaches that simultaneously target HIV reservoirs and lymphoma\u2014including allogeneic hematopoietic stem cell transplantation, chimeric antigen receptor T-cell therapy, and immune checkpoint inhibitors\u2014show promise but face substantial challenges. There is an urgent need to develop accessible strategies that can both eradicate HIV reservoirs and mitigate lymphoma risk. Such efforts may ultimately enable a \u201cdouble cure\u201d for PLWH with lymphoma, offering new hope against this life-threatening comorbidity. This review summarizes the potential links between HIV reservoirs and HIV-associated lymphoma and outlines emerging therapeutic avenues toward achieving a double cure.<\/jats:p>","DOI":"10.1128\/mmbr.00104-25","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T13:00:26Z","timestamp":1759842026000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["HIV reservoirs in lymphomagenesis: hidden driver in the era of viral suppression?"],"prefix":"10.1128","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-0957","authenticated-orcid":false,"given":"Yaoguang","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Center for HIV\/AIDS, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xiao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/023rhb549","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hematology-Oncology, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengting","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Center for HIV\/AIDS, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-9879","authenticated-orcid":true,"given":"Fujie","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Center for HIV\/AIDS, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"UNAIDS. 2023. 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