Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study

• Published in: Clinical infectious diseases 2024-08
• Main Authors: Gakuru, Jane, Kagimu, Enock, Dai, Biyue, Okurut, Samuel, Nsangi, Laura, Bahr, Nathan C, Okirwoth, Michael, Namuju, Olivie C, Jarvis, Joseph N, Lawrence, David S, Ahimbisibwe, Cynthia, Ellis, Jayne, Tadeo, Kizza Kandole, Boulware, David R, Meya, David B, Tugume, Lillian
• Format: Article
• Language: English
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciae413

In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of 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. 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. 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 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%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). 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.