This series of review articles outlines the complex cause of HIV-related cardiovascular diseases (CVDs) particularly the interactions of viral factors, complications of antiviral therapy such as metabolic derangement, and chronic systemic inflammation. These factors, directly stemming from chronic HIV infection, are important in the pathogenesis of HIV-related CVD. Addressing each issue has likely underpinned the improved morbidity and increased life expectancy enjoyed by patients in the modern era of HIV management. The global management of HIV-related CVD may, however, be simpler than previously imagined, as the disease likely follows a pathway shared by multiple systemic diseases. Other chronic systemic diseases, including diabetes, rheumatoid arthritis, and autoimmune disease, share numerous pathophysiological mechanisms with HIV and provoke similar cardiac complications. CVD risk management in patients living with HIV (PLHIV) may be optimized by drawing upon existing knowledge of chronic systemic diseases which may open up new concepts in treatment and address the current shortfalls in cardiovascular management of PLHIV.