The acceptability of the AMBITION-cm treatment regimen for HIV-associated cryptococcal meningitis: Findings from a qualitative methods study of participants and researchers in Botswana and Uganda

Abstract

Background The AMBITION-cm trial for HIV-associated cryptococcal meningitis demonstrated that a single, high-dose of liposomal amphotericin (AmBisome) plus 14-days of oral flucytosine and fluconazole was non-inferior in terms of all-cause mortality to 7-days of amphotericin B deoxycholate and flucytosine followed by 7-days of fluconazole (Control). The AmBisome regimen was associated with fewer adverse events. We explored the acceptability of the AmBisome regimen from the perspective of participants and providers. Methods We embedded a qualitative methods study within the AMBITION-cm sites in Botswana and Uganda. We conducted in-depth interviews with trial participants, surrogate decision makers, and researchers and combined these with direct observations. Interviews were transcribed, translated, and analysed thematically. Results We interviewed 38 trial participants, 20 surrogate decision makers, and 31 researchers. Participant understanding of the trial was limited; however, there was a preference for the AmBisome regimen due to the single intravenous dose and fewer side effects. More time was required to prepare the single AmBisome dose but this was felt to be acceptable given subsequent reductions in workload. The AmBisome regimen was reported to be associated with fewer episodes of rigors and thrombophlebitis and a reduction in the number of intravenous cannulae required. Less intensive monitoring and management was required for participants in the AmBisome arm. Conclusions The AmBisome regimen was highly acceptable, being simpler to administer despite the initial time investment required. The regimen was well tolerated and associated with less toxicity and resultant management. Widespread implementation would reduce the clinical workload of healthcare workers caring for patients with HIV-associated cryptococcal meningitis.

Once-Weekly Liposomal Amphotericin B Use for Maintenance and Consolidation Phase Treatment of Cryptococcal Meningitis in Patients With AIDS

“…We opted for LampB due to its favorable side effects profile, as highlighted in the WHO 2022 guidelines [ 1 , 2 ]. Liposomal formulation of amphotericin is preferred as part of the induction regimen based on the Ambisome Therapy Induction Optimization (AMBITION-CM) trial [ 3 , 4 ] which showed similar efficacy of liposomal formulation with less chance of developing kidney damage. After the initiation of the treatment, the patient developed acute kidney injury (AKI) and persistent electrolyte derangements (hypomagnesemia and hypokalemia).…”

How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus–Associated Cryptococcal Meningitis to High-Income Settings?

“…In a retrospective analysis of 24 151 patients with HIV-associated cryptococcal meningitis who were treated in the United States between 1997 and 2009, the average hospitalization cost was calculated to be $15 708 per patient [ 37 ]; these costs have increased significantly since that time [ 38 ]. In addition, a social science substudy of the AMBITION trial points to a clear preference on the part of participants and healthcare providers for the single-dose regimen [ 39 ]. Given their vulnerable status and ongoing nosocomial infection risks, patients in high-income countries with less severe disease may also welcome and benefit from the simplified delivery of treatment and the possibility of earlier discharge with the AMBITION regimen.…”

Lived experience of people with cryptococcal meningitis: A qualitative study

“…The few qualitative-methods studies on CM, exploring aspects such as acceptability of different CM regimens, have been done within the context of clinical trials. 17 , 18 , 19 , 20 Thus there is a gap in understanding the lived experience of people with CM outside clinical trials. Hence, we explored the experiences of people living with HIV-associated CM in routine care using qualitative methods.…”