In 2002 we reported the occurrence of avascular necrosis of bone (usually the hip) in 15 asymptomatic patients with HIV disease. We have continued to follow these asymptomatic patients, and have also enrolled a cohort of approximately 40 patients with symptomatic osteonecrosis. This includes patients who were being followed in our clinic as well as patients referred from community physicians. The occurrence of pain and functional disability is being assessed, with the primary endpoint being the time to joint replacement. The radiographic evolution of hip lesions is also being evaluated by yearly MRIs. In 2007, we published a summary of our experiences describing the incidence of osteonecrosis in our clinic population as well as the proportion of patients that needed to go on to surgical repair/joint replacement. We found that most asymptomatic patients remained asymptomatic, though a small proportin developed symptoms and needed hip replacement. We also found that among patients with symptomatic ostoenecrosis, the median time to hip replacement was under one year. We recently found that D-dimer and hsCRP, important markers of inflammation in HIV-infected patients, were significantly higher in patients with osteonecrosis compared to an HIV-infected control population at the time of diagnosis as well as approximately 6 months later, and that hsCRP was also elevated approximately 6 months prior to the diagnosis of osteonecrosis, suggesting that ongoing inflammation is a risk factor that may contribute to the development of osteonecrosis. The latter study has been submitted for publication. We are continuing to enroll patients with symptomatic disease and to follow these patients long term, as it is one of the largest such cohorts being followed. This type of long-term follow-up is necessary in order to determine the long term natural history and clinical relevance of findings.