Here we describe the pro-inflammatory state of HIV-1 infection that leads to increased risk of cardiovascular disease, the role of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in HIV-1 infection, the role of the NLRP3 inflammasome in cardiovascular disease (CVD), and outline a model whereby HIV-1 infection can lead to atherosclerotic disease through NLRP3 inflammasome activation. The gene discussed is NLRP3; the disease is HIV-1 infection.