by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
September 10, 2024
Featured Literature:
Gakuru J, Kagimu E, Dai B, et al. 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. Clin Infect Dis. 2024 Aug 24:ciae413. doi:10.1093/cid/ciae413.
This study evaluated outcomes after implementation of the AMBITION-cm cryptococcal treatment regimen in routine care in Uganda, which was the largest recruiting country for the initial AMBITION-cm trial (342 trial participants were enrolled from two trial sites in Uganda, with 171 randomized to the AMBITION-cm intervention arm). For this analysis, 179 observational cohort participants were enrolled across three hospitals from September 2022 to October 2023. Adults with cryptococcal meningitis (diagnosed by CSF CrAg lateral flow assay) or relapse of meningitis (diagnosed using CSF fungal culture only) received a single 10mg/kg dose of liposomal amphotericin B plus 14-days of flucytosine 100mg/kg/day and fluconazole 1200mg/day for induction; outcomes were compared to those from the original trial participants. 144/179 (80.4%) had available 10-week outcome data. After adjusting for baseline differences in demographics, 10-week survival did not differ between groups (adjusted Hazard Ratio = 1.17; p=.51) after adjusting for age, altered mental status, ART status, fungal burden, CSF pleocytosis with >5 white cells/μL, and anemia. The mean rate of CSF cryptococcal clearance was similar between groups, and median duration of hospitalization was 11 days for the observational cohort. 52% of observational cohort participants had at least one follow-up laboratory monitoring test during the 2-week induction period, with 4/93 (4%) developing Grade 3 or 4 laboratory adverse events.
Author’s Commentary:
In 2022, the World Health Organization’s cryptococcal guidelines were updated to recommend the AMBITION-cm regimen as preferred therapy for PWH, and this is an early “real world” study describing implementation outcomes. Despite an approximate 20% lost-to-follow-up rate and key baseline differences in the observational cohort compared with original trial participants (i.e., the observational cohort had a higher proportion of ART-naïve PWH, higher proportion with sterile CSF fungal culture at meningitis diagnosis, and lower initial fungal burden in participants with non-sterile CSF cultures), findings from this study are very encouraging. Other important contextual public health elements should be noted, namely widespread implementation of CrAg screening programs, which may not be generalizable to other settings. Authors also note the importance of return precautions counseling and timely follow-up when hospital discharge is being considered; although concerns about premature discharge with uncontrolled intracranial pressure did not manifest in this analysis, appropriate infrastructures and protocols should be in place to ensure close early monitoring.
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