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Non-traumatic bowel perforation caused by cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections has become rare among patients with acquired immunodeficiency syndrome (AIDS) in the era of combination antiretroviral therapy (cART); however, CMV-associated and MAC-related immune reconstitution inflammatory syndrome (IRIS) has subsequently emerged owing to the wide use of integrase inhibitor-based regimens. Here we report a case of spontaneous perforation of the jejunum in a patient with human immunodeficiency virus (HIV) infection with good compliance to cART.