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.

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. Author summary: The AMBIsome Therapy Induction OptimisatioN (AMBITION-cm) clinical trial found that a single, high-dose, intravenous liposomal amphotericin B (AmBisome) based regimen for HIV-associated cryptococcal meningitis was non-inferior to the WHO recommended first-line treatment which includes seven daily doses of intravenous amphotericin B deoxycholate. The AmBisome regimen was also associated with fewer adverse events. In addition to the clinical efficacy data it is important to consider how acceptable the AmBisome regimen was from the perspectives of those who received the regimen as well as the healthcare workers administering it. To do this we conducted a qualitative methods study of in-depth interviews with AMBITION-cm trial participants, surrogate decision makers, and researchers working on the trial. These interviews were combined with direct observations of the research process and analysed thematically. The trial participants were often severely unwell and therefore the understanding of the trial was limited; however, the AmBisome regimen was generally preferred due to the single intravenous dose and fewer side effects. Researchers strongly preferred the AmBisome regimen which took less time to administer overall and was also associated with fewer side effects. We conclude that these findings complement the efficacy data from the clinical trial to support widespread implementation of the regimen. [ABSTRACT FROM AUTHOR]