HIV-infected individuals have a 1.5- to 2-fold increased risk of developing cardiovascular disease (CVD). Despite effective antiretroviral therapy (ART), chronic inflammation remains a key factor in the development of CVD in people living with HIV (PLWH). Factors such as the HIV reservoir, coinfections, clonal hematopoiesis of indeterminate potential (CHIP), microbial translocation, and ART contribute to this chronic inflammation. Macrophages, which harbor latent HIV, play a significant role in atherosclerosis by secreting inflammatory cytokines that promote endothelial dysfunction and atheroma formation. HIV-1 primes the NLRP3 inflammasome, increasing IL-1β expression, which is important for cardiovascular outcomes. HIV proteins like Nef inhibit cholesterol efflux in monocytes and macrophages, promoting foam cell formation and atherosclerosis. The immune system, both innate and adaptive, contributes to systemic and vascular inflammation. PLWH have persistent systemic inflammation, leading to multiple comorbidities, including CVD. The REPRIEVE study showed that pitavastatin reduced major cardiovascular events in PLWH. Atherosclerosis in PLWH is a complex chronic inflammatory disease involving endothelial dysfunction, lipid accumulation, and immune cell infiltration. HIV and its treatment can impact CVD risk factors, with PLWH having a higher risk of CVD than the general population. Endothelial dysfunction is an early precursor to atherosclerosis, with HIV-induced dysfunction leading to increased vascular inflammation. HIV also affects lipid metabolism, contributing to dyslipidemia and atherosclerosis. Plaque progression involves the recruitment of inflammatory immune cells and alterations in vascular smooth muscle cells. HIV can hinder cholesterol efflux, leading to foam cell formation. Noncalcified and calcified plaques differ in their characteristics and risk profiles. The innate and adaptive immune systems play critical roles in atherosclerosis, with monocytes/macrophages, dendritic cells, and T cells contributing to inflammation and plaque formation. CHIP, a condition associated with mutations in genes like DNMT3A and ASXL1, increases atherosclerotic CVD risk. HIV infection of dendritic cells can promote atherosclerosis. Trained immunity, a form of innate immune memory, may contribute to atherosclerosis in PLWH. T cells and B cells are involved in atherosclerosis, with CD4+ and CD8+ T cells playing key roles. HIV primarily infects CD4+ T cells, leading to immune activation and increased CVD risk. T cell activation and senescence are associated with subclinical atherosclerosis in PLWH. The role of the immune system in CVD among PLWH is complex, involving multiple factors that contribute to atherosclerosis and cardiovascular outcomes.HIV-infected individuals have a 1.5- to 2-fold increased risk of developing cardiovascular disease (CVD). Despite effective antiretroviral therapy (ART), chronic inflammation remains a key factor in the development of CVD in people living with HIV (PLWH). Factors such as the HIV reservoir, coinfections, clonal hematopoiesis of indeterminate potential (CHIP), microbial translocation, and ART contribute to this chronic inflammation. Macrophages, which harbor latent HIV, play a significant role in atherosclerosis by secreting inflammatory cytokines that promote endothelial dysfunction and atheroma formation. HIV-1 primes the NLRP3 inflammasome, increasing IL-1β expression, which is important for cardiovascular outcomes. HIV proteins like Nef inhibit cholesterol efflux in monocytes and macrophages, promoting foam cell formation and atherosclerosis. The immune system, both innate and adaptive, contributes to systemic and vascular inflammation. PLWH have persistent systemic inflammation, leading to multiple comorbidities, including CVD. The REPRIEVE study showed that pitavastatin reduced major cardiovascular events in PLWH. Atherosclerosis in PLWH is a complex chronic inflammatory disease involving endothelial dysfunction, lipid accumulation, and immune cell infiltration. HIV and its treatment can impact CVD risk factors, with PLWH having a higher risk of CVD than the general population. Endothelial dysfunction is an early precursor to atherosclerosis, with HIV-induced dysfunction leading to increased vascular inflammation. HIV also affects lipid metabolism, contributing to dyslipidemia and atherosclerosis. Plaque progression involves the recruitment of inflammatory immune cells and alterations in vascular smooth muscle cells. HIV can hinder cholesterol efflux, leading to foam cell formation. Noncalcified and calcified plaques differ in their characteristics and risk profiles. The innate and adaptive immune systems play critical roles in atherosclerosis, with monocytes/macrophages, dendritic cells, and T cells contributing to inflammation and plaque formation. CHIP, a condition associated with mutations in genes like DNMT3A and ASXL1, increases atherosclerotic CVD risk. HIV infection of dendritic cells can promote atherosclerosis. Trained immunity, a form of innate immune memory, may contribute to atherosclerosis in PLWH. T cells and B cells are involved in atherosclerosis, with CD4+ and CD8+ T cells playing key roles. HIV primarily infects CD4+ T cells, leading to immune activation and increased CVD risk. T cell activation and senescence are associated with subclinical atherosclerosis in PLWH. The role of the immune system in CVD among PLWH is complex, involving multiple factors that contribute to atherosclerosis and cardiovascular outcomes.