BACKGROUND: In 2022, the World Health Organization (WHO) recommended a single 10 mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda. METHODS: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites. RESULTS: During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%
95% confidence interval [CI]: 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%
95% CI: 65.2%-78.8%
absolute risk difference = -3.1%
95% CI: -13.1% to 6.9%
P = .61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day
P = .80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144). CONCLUSIONS: The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.