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Complexities in the treatment of coinfection with HIV, hepatitis B, hepatitis C, and tuberculosis. HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) are commonly encountered blood-borne infectious microorganisms. Infection with these viruses typically requires long-lasting drug therapy. Coinfections, especially with tuberculosis, pose a challenge to the creation of a regimen with adequate efficacy and minimal drug-drug interactions and adverse effects. We present the case of a young man with a history of intravenous drug misuse who was diagnosed with disseminated tuberculosis and with a triple infection with HBV, HCV, and HIV. The treatment for tuberculosis was initiated first, followed 2 months later by antiretrovirals that were effective against both HIV and HBV. After 9 months of antitubercular therapy, HCV was successfully treated with 12 weeks of oral direct-acting antivirals. We describe the challenges faced in formulating a therapeutic plan for such patients and discuss the various drug interactions that can arise between antitubercular drugs, antiretrovirals, anti-HBV drugs, and direct-acting antivirals against HCV.