Cryptococcal Infection in Advanced HIV-Associated Immunosuppression—Case Series

Background and Clinical Significance: Cryptococcal meningitis remains a life-threatening complication of advanced HIV infection. Its recognition can be challenging when neurological manifestations are nonspecific or cerebrospinal fluid inflammation is limited. This case series illustrates the diagnostic variability and therapeutic challenges encountered in five patients managed at a regional HIV/AIDS center in northeastern Romania. Case Presentation: Five men aged 26–69 years were hospitalized between November 2022 and March 2025 with HIV-associated cryptococcal disease involving the central nervous system. All had profound immunosuppression, with CD4+ T-cell counts of 6–31 cells/mm3. Clinical manifestations included headache, confusion, altered consciousness, and focal neurological deficits. Cerebrospinal fluid opening pressures were elevated, while inflammatory findings ranged from lymphocytic pleocytosis to an almost acellular profile. Microbiological investigations included direct microscopy, fungal culture, and molecular testing, according to availability. In one patient, culture confirmed Cryptococcus neoformans despite negative India ink microscopy and absent documented pleocytosis. Antifungal treatment included liposomal amphotericin B and fluconazole-based regimens, with treatment selection constrained by drug availability and organ dysfunction. Three cases had fatal outcomes during hospitalization. Conclusions: Cryptococcal meningitis should remain a diagnostic consideration in profoundly immunosuppressed patients with neurological symptoms, even when initial microscopy is negative or cerebrospinal fluid inflammation is minimal. These cases emphasize the importance of complementary microbiological investigations, assessment and management of intracranial pressure, reliable access to recommended antifungal regimens, and appropriate timing of antiretroviral therapy.