Fungi have been reported since the 1980s in patients with HIV/AIDS as primary drivers for mortality in this population [1, 2]. Schizophyllum commune is a fungus uncommonly described in humans because of the difficulties encountered in the laboratory identification of this agent [3]. This fungus is ubiquitous and grows on trees and decaying wood, being widely distributed in the environment [4]. Infection occurs by inhalation of the basidiospores, with bronchopul-monary disease and sinusitis accounting for 94% of cases. Extrapulmonary dissemination was described and the brain was the most affected organ, manifesting as brain abscess [5]. In HIV-infected patients, manifestations were related to chronic sinusitis [3, 6]. Herein, we report the first case of bloodstream infection with S. commune in an HIV-infected patient. A 49-year-old Brazilian man who had received HIV diagnosis a few days before was admitted to our hospital with mild dyspnea, chronic productive cough, weight loss, headache, and fever. The diagnosis of pulmonary tuberculosis was ascertained by direct examination of sputum samples for acid-fast bacilli (AFB) and treatment was started with rifampicin, isoniazid, ethambutol, and pyrazi-namide. The patient was antiretroviral therapy (ART) naïve, with a baseline total CD4+ lym-phocyte (TCD4+) count of 106 cells/μl and an HIV viral load (VL) of 180,990 copies/ml (5.3 log10). He underwent a brain computed tomography (CT) scan and lumbar puncture (LP) due to headache and neck stiffness found on physical examination. The initial cerebrospinal fluid (CSF) analysis revealed 166 cells/mm 3 (95% mononuclear), protein 71.7 mg/dl, normal glucose levels, and negative direct microscopy for fungi, AFB, or other bacteria. Cultures were negative after appropriate incubation periods. The brain CT scan revealed a hypodense lesion in the right caudate nucleus suggestive of encephalomalacia from a previous lesion. Steroids were added to the antituberculous regimen with the consideration of tuberculosis meningitis, and the patient was discharged. ART was initiated in the outpatient unit with zidovudine, lamivudine, and efavirenz. After 2 weeks, the patient was readmitted to the hospital with severe headache, disorientation, and paraparesis. A new CT scan showed several new contrast-enhancing lesions located in both cerebral hemispheres (Fig 1A), associated with mass effect. PLOS Neglected Tropical Diseases | https://doi.