Opportunistic infections remain a major cause of morbidity and mortality in individuals with advanced human immunodeficiency virus (HIV) disease. Although central nervous system opportunistic infections are common, simultaneous infection by multiple nonbacterial pathogens is rare. We report a 46-year-old man with advanced HIV disease and profound immunosuppression who presented with gastrointestinal symptoms and altered mental status. Brain magnetic resonance imaging initially suggested cerebral toxoplasmosis; however, persistent symptoms and new lesions despite trimethoprim-sulfamethoxazole prompted further investigation. Cerebrospinal fluid analysis and stereotactic brain biopsy confirmed concurrent central nervous system coinfection with Toxoplasma gondii , Cryptococcus neoformans , and cytomegalovirus. Extraneurological involvement included cytomegalovirus colitis and chorioretinitis. Combination therapy with ganciclovir, amphotericin B, fluconazole, and trimethoprim-sulfamethoxazole resulted in marked clinical improvement, allowing discharge after 59 days. This case highlights the importance of maintaining a broad differential diagnosis and pursuing advanced diagnostics when empiric therapy fails in advanced HIV disease.
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Ortiz et al. (2026) studied this question.
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