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Human Immunodeficiency Virus (HIV) infection and use of protease inhibitors have been associated with accelerated atherosclerosis. Increased rates of coronary in-stent restenosis are reported in these patients. There is limited data available on peripheral vascular disease interventions on these patients. Herein we report an aggressive subclavian in-stent restenosis with an unexpected response to balloon angioplasty treatment with a large, mobile tissue flap formation and its treatment with another stent.