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Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial.

Lawrence, David S, Muthoga, Charles, Meya, David B, Tugume, Lillian, Williams, Darlisha, Rajasingham, Radha, Boulware, David R, Mwandumba, Henry ORCID: https://orcid.org/0000-0003-4470-3608, Moyo, Melanie, Dziwani, Eltas N, Maheswaran, Hendramoorthy, Kanyama, Cecilia, Hosseinipour, Mina C, Chawinga, Chimwemwe, Meintjes, Graeme, Schutz, Charlotte, Comins, Kyla, Bango, Funeka, Muzoora, Conrad, Jjunju, Samuel, Nuwagira, Edwin, Mosepele, Mosepele, Leeme, Tshepo, Ndhlovu, Chiratidzo E, Hlupeni, Admire, Shamu, Shepherd, Boyer-Chammard, Timothée, Molloy, Síle F, Youssouf, Nabila, Chen, Tao ORCID: https://orcid.org/0000-0002-5489-6450, Shiri, Tinevimbo, Jaffar, Shabbar ORCID: https://orcid.org/0000-0002-9615-1588, Harrison, Thomas S, Jarvis, Joseph N and Niessen, Louis ORCID: https://orcid.org/0000-0002-8639-5191 (2022) 'Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial.'. Lancet Global Health, Vol 10, Issue 12, e1845-e1854.

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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.

Item Type: Article
Corporate Authors: AMBITION Study Group
Subjects: WA Public Health > WA 30 Socioeconomic factors in public health (General)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 200 Bacterial infections (General or not elsewhere classified)
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
WL Nervous System > WL 20 Research (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1016/S2214-109X(22)00450-8
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 03 Jan 2023 10:08
Last Modified: 14 Jun 2023 11:37
URI: https://archive.lstmed.ac.uk/id/eprint/21584

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