Incidence, reasons, and outcomes of rehospitalization among adults with HIV-related cryptococcal meningitis in Uganda: a post-hoc analysis of a prospective cohort

While advances in treatment for cryptococcosis have improved survival, post-discharge outcomes such as rehospitalization remain poorly understood. We characterized the incidence, reason(s), and outcomes of rehospitalization after cryptococcal meningitis. We conducted a post hoc review of four clinical trials conducted from 2015 to 2024 at Mulago, Mbarara, and Kiruddu Hospitals in Uganda. We followed adults with HIV-related cryptococcal meningitis discharged alive after initial hospitalization for > 10 weeks. Of 1055 diagnosed participants, 787 were discharged alive. The median CD4 cell count was 21 cells/µL (IQR, 8–58), and 45% were ART-experienced. Overall, 26.6% (209/787) experienced either rehospitalization (17%, n = 133/787) or death (13%, n = 101/787) within 10 weeks. Among 654 participants who did not report rehospitalization, 11.6% (76/654) died by 10 weeks without rehospitalization; among 133 participants who were rehospitalized, 18% (25/133) died during or after rehospitalization. The median time from initial discharge to rehospitalization was 20 days (IQR: 10, 36). The main reasons for 133 rehospitalizations were: meningitis due to culture-positive relapse, paradoxical immune reconstitution inflammatory syndrome, or elevated intracranial pressure ( n = 92); tuberculosis ( n = 26); other opportunistic infections ( n = 39); hematologic disorders ( n = 21); kidney/electrolyte disorders ( n = 29); malignancy ( n = 9); other conditions ( n = 23). There were no risk factors identified for rehospitalization. However, older age increased the risk of death, while higher weight and Glasgow Coma Scale scores were protective. One quarter of adults with HIV-related cryptococcal meningitis who survived initial hospitalization experienced rehospitalization or death within 10 weeks following discharge due to a variety of meningitis and AIDS-related complications. No risk factors for rehospitalization were identified. This was a sub-study and a post-hoc analysis of a prospective cohort assembled from four clinical trials: ASTRO (NCT01802385, 28 Feb 2013), AMBITION (ISRCTN72509687, 13 July 2017), ENACT (NCT04031833, 01 January 2019), and FLOOR(NCT06414512, 09 April 2024).