HIV infection causes progressive immune dysfunction and impairs B-cell surveillance, leading to uncontrolled B-cell activation and proliferation. This section examines the mechanisms by which immune dysregulation contributes to the development of DLBCL. Co-infections with oncogenic viruses, particularly EBV and HHV-8, significantly increase the risk of DLBCL in PLWH. This section explores the role of these viruses in DLBCL pathogenesis and their interaction with HIV. Additional viral co-infections, such as Human Herpesvirus-8 (HHV- 8), hepatitis C virus (HCV), and Human T-cell Lymph Tropic Virus Type 1 (HTLV-1), have been implicated in DLBCL development in PLWH. This section discusses their potential contributions to lymphomagenesis [3-5]. HIV-induced immunodeficiency compromises immune surveillance mechanisms, allowing the expansion of transformed B-cell clones and the escape of malignant cells from immune control. This section discusses the consequences of impaired tumour surveillance in DLBCL development.