Factors associated with 90-day mortality in adults with cryptococcal meningoencephalitis across HIV, solid organ transplant, and non-HIV, non-transplant populations

Abstract Purpose Predictors of mortality in cryptococcal meningoencephalitis (CM) across HIV, solid organ transplant (SOT), and non-HIV, non-transplant (NHNT) populations remain incompletely defined. We compared clinical characteristics and 90-day mortality across host groups and evaluated factors associated with mortality. Methods Adults with CM were identified in TriNetX (2003–2024) using ICD-10-CM codes or cerebrospinal fluid cryptococcal antigen or DNA evidence. Analyses were restricted to amphotericin B-treated patients to improve diagnostic specificity. Patients with available host-group information were categorized as HIV, SOT, or NHNT. Multivariable Cox regression evaluated 90-day mortality, adjusting for age, sex, ethnicity, Charlson Comorbidity Index, pre-index glucocorticoid exposure, and calendar year. Results Among 650 patients in the final analytic cohort, 26.0% had HIV, 22.2% were SOT recipients, and 51.8% were NHNT. Overall 90-day mortality was 19.5% (n=127), and was highest among NHNT patients (23.1%), followed by SOT recipients (19.4%) and patients with HIV (12.4%). Non-survivors were older and more frequently had neoplasms, hematologic malignancy, aplastic anemia, and liver disease. NHNT status was associated with higher mortality than HIV in unadjusted analysis (HR 1.98, 95% CI 1.22–3.20). In the multivariable model ( n  = 608, 113 deaths), this association was attenuated (aHR 1.16, 95% CI 0.36–3.69), while advancing age remained independently associated with mortality (aHR 1.02/year, 95% CI 1.01–1.04). Conclusions NHNT adults had the highest crude mortality, but this association was attenuated after adjustment. Advancing age remained independently associated with mortality, while the independent association between host group and mortality remained uncertain.