Hoffa's syndrome involves inflammation of the infrapatellar fat pad secondary to direct trauma or microtrauma. Alternative sources of inflammation of Hoffa's fat pad include synovial processes such as pigmented villonodular synovitis (PVNS) and osteochondromatosis. Recently, a few cases of inflammation of Hoffa's fat pad secondary to human immunodeficiency virus (HIV) have been described. Our case presents an HIV patient with Hoffa's fat-pad inflammation as well as prefemoral fat-pad edema, posterior soft-tissue inflammation, and bone infarction. Since patients with HIV now live longer due to improved treatment regimens, it is important for radiologists to recognize HIV-related musculoskeletal manifestations, such as non-neoplastic inflammation in Hoffa's fat pad (as seen in our patient).