Abstract
Background: HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis. Methods: The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed. Findings: The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314–1424) in the AmBisome group and $1237 (1181–1293) in the control group. The incremental cost-effectiveness ratio was $128 (59–257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15–275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda. Interpretation: The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays. Funding: European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research. Translations: For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e1845-e1854 |
| Journal | The Lancet Global Health |
| Volume | 10 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2022 |
Bibliographical note
Funding Information:We thank all trial participants, their families, and carers, as well as all the clinical, laboratory, and administrative staff at all sites who were not directly involved in the trial and the cost-effectiveness analysis; Andrew Nunn, Sayoki Mfinanga, Robert Peck, and William Powderly for serving on the data and safety monitoring committee; and John Perfect, Andrew Kambugu, Saidi Kapiga, and Douglas Wilson for serving on the trial steering committee. This study was funded by a grant through the European Developing Countries Clinical Trials Partnership, supported by the Swedish International Development Cooperation Agency (TRIA2015–1092), and the UK Department of Health and Social Care, the UK Foreign Commonwealth and Development Office, the UK Medical Research Council, and the Wellcome Trust, through the Joint Global Health Trials scheme (MR/P006922/1). This work was also funded by the National Institute for Health Research through a Global Health Research Professorship to JNJ (RP-2017–08-ST2–012), using UK aid from the UK Government to support global health research. CMut was supported by a Wellcome Trust International Masters Fellowship (212638/Z/18/Z). GM was supported by the Wellcome Trust (098316, 214321/Z/18/Z, and 203135/Z/16/Z), and the South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation of South Africa (grant number 64787). RR is supported by the US National Institute of Allergy and Infectious Diseases (K23AI138851). This research was funded in part by the Wellcome Trust. The AmBisome was donated by Gilead Sciences. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The views expressed in this publication are those of the author(s) and not necessarily those of the funders.
Funding Information:
We thank all trial participants, their families, and carers, as well as all the clinical, laboratory, and administrative staff at all sites who were not directly involved in the trial and the cost-effectiveness analysis; Andrew Nunn, Sayoki Mfinanga, Robert Peck, and William Powderly for serving on the data and safety monitoring committee; and John Perfect, Andrew Kambugu, Saidi Kapiga, and Douglas Wilson for serving on the trial steering committee. This study was funded by a grant through the European Developing Countries Clinical Trials Partnership, supported by the Swedish International Development Cooperation Agency (TRIA2015–1092), and the UK Department of Health and Social Care, the UK Foreign Commonwealth and Development Office, the UK Medical Research Council, and the Wellcome Trust, through the Joint Global Health Trials scheme (MR/P006922/1). This work was also funded by the National Institute for Health Research through a Global Health Research Professorship to JNJ (RP-2017–08-ST2–012), using UK aid from the UK Government to support global health research. CMut was supported by a Wellcome Trust International Masters Fellowship (212638/Z/18/Z). GM was supported by the Wellcome Trust (098316, 214321/Z/18/Z, and 203135/Z/16/Z), and the South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation of South Africa (grant number 64787). RR is supported by the US National Institute of Allergy and Infectious Diseases (K23AI138851). This research was funded in part by the Wellcome Trust. The AmBisome was donated by Gilead Sciences. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The views expressed in this publication are those of the author(s) and not necessarily those of the funders.
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
