A 43-year-old Hispanic male presented to the hospital with frontal headache, fever, nausea, and vomiting ongoing for 2 weeks. His past medical history was significant for herpes zoster ophthalmicus two years ago. His vital signs on admission were within normal limits. Neurological examination was remarkable for mild cervical stiffness and pain with neck motion. No focal signs were noted. Laboratory studies were remarkable for normal white blood cell count (WBC: 6.7 k/uL), low hemoglobin (10.8 g/dL), and normal platelet count (172 K/uL). Rapid HIV test was reactive. Complete chemistry panel was within normal limits. Chest X-ray did not show any abnormalities. Due to a high suspicion for meningitis, the patient underwent a brain computed tomography (CT) followed by a lumbar puncture. Brain CT scan did not disclose any abnormalities. Cerebrospinal fluid (CSF) analysis revealed high WBC count (73 leukocytes/mm3) with lymphocytic predominance (96%), high protein (112 mg/dL), and low glucose (37 mg/dL). The patient was started on ceftriaxone, vancomycin, and acyclovir empirically. Later on, studies revealed a CD4 count of 83 cells/uL and a HIV viral load of 51,080 copies/mL. Serum RPR was reactive with a titer of 1 : 1024 dils. VDRL from CSF was also reactive. Based on these results, the patient was diagnosed with neurosyphilis and intravenous penicillin was started. At this point, ceftriaxone, vancomycin, and acyclovir were discontinued. Over the following three days, the patient reported worsening headache and neck pain accompanied by nausea and vomiting. He also complained of slurred speech and visual hallucinations. Due to lack of response to neurosyphilis treatment, a magnetic resonance imaging was ordered. It showed T2 and flair hyperintense signal involving the left middle cerebral peduncle and vermis and in the right cerebellar hemisphere medial aspect. Lumbar puncture was repeated and CSF analysis showed a higher number of WBCs (267 leukocytes/mm3) with lymphocytic predominance (74%), low glucose (8 mg/dL), and high protein (94 mg/dL). Cryptococcus antigen from CSF was positive with a titer of 1 : 640 dils. India ink stain and fungal culture were negative. He was started on amphotericin B lipid complex and flucytosine for cryptococcal meningitis. The patient improved clinically over the following week. After two weeks of treatment with amphotericin and flucytosine, he was switched to oral fluconazole 400 mg daily for consolidation therapy. He also completed two weeks of intravenous penicillin for neurosyphilis and was discharged in stable condition with resolution of headaches. After 2 weeks, he started antiretroviral therapy with tenofovir alafenamide/emtricitabine and darunavir-ritonavir. At 1-month follow-up, he complained of malaise and dizziness along with slurred speech and left hand clumsiness. On physical exam, he had an ataxic gait and saccadic eye movements. A repeat MRI showed improvement of leptomeningeal enhancement supratentorially but progression of leptomeningeal enhancement and T2/FLAIR signal abnormality within the posterior fossa (Figure 1). The patient was readmitted to the hospital and underwent a new lumbar puncture. Opening pressure was elevated (26 cm H2O). CSF analysis showed 2 WBCs and normal glucose and protein. India ink stain revealed rare encapsulated yeasts. Cryptococcus antigen from CSF was 1 : 80 dils. Fungal culture did not show any growth. He was restarted on induction therapy with amphotericin B 1 mg/kg/day and flucytosine for a possible relapse of cryptococcal meningitis. After 2 weeks of treatment, his symptoms improved significantly and he was discharged on oral fluconazole 800 mg daily for consolidation therapy. Two weeks after discharge, CSF culture from recent hospital admission grew Mycobacterium tuberculosis. Identification was confirmed by PCR restriction analysis- (PRA-) hsp65. Antibiogram showed resistance only to streptomycin (Table 1). The patient was started on antituberculosis therapy with isoniazid, rifabutin, pyrazinamide, ethambutol, and cycloserine. His antiretroviral therapy was modified to avoid drug interactions with antituberculosis regimen. Darunavir-ritonavir was switched to dolutegravir and he continued with tenofovir alafenamide/emtricitabine. Given his recent episode of possible Cryptococcus relapse, he continued with a high fluconazole dose (800 mg daily) for a prolonged consolidation therapy.