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.

The AMBITION Study Group; David S. Lawrence; Charles Muthoga; David B. Meya; Lillian Tugume; Darlisha Williams; Radha Rajasingham; David R. Boulware; Henry Mwandumba; Melanie Moyo; Eltas N. Dziwani; Hendramoorthy Maheswaran; Cecilia Kanyama; Mina C. Hosseinipour; Chimwemwe Chawinga; Graeme Meintjes; Charlotte Schutz; Kyla Comins; Funeka Bango; Conrad Muzoora; Samuel Jjunju; Edwin Nuwagira; Mosepele Mosepele; Tshepo Leeme; Chiratidzo E. Ndhlovu; Admire Hlupeni; Shepherd Shamu; Timothée Boyer-Chammard; Síle F. Molloy; Nabila Youssouf; Tao Chen; Tinevimbo Shiri; Shabbar Jaffar; Thomas S. Harrison; Joseph N. Jarvis; Louis Niessen

doi:10.1016/s2214-109x(22)00450-8

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.

The AMBITION Study Group
, David S. Lawrence
, Charles Muthoga
, David B. Meya
, Lillian Tugume
, Darlisha Williams
, Radha Rajasingham
, David R. Boulware
, Henry Mwandumba
, Melanie Moyo
, Eltas N. Dziwani
, Hendramoorthy Maheswaran
, Cecilia Kanyama
, Mina C. Hosseinipour
, Chimwemwe Chawinga
, Graeme Meintjes
, Charlotte Schutz
, Kyla Comins
, Funeka Bango
, Conrad Muzoora

Samuel Jjunju, Edwin Nuwagira, Mosepele Mosepele, Tshepo Leeme, Chiratidzo E. Ndhlovu, Admire Hlupeni, Shepherd Shamu, Timothée Boyer-Chammard, Síle F. Molloy, Nabila Youssouf, Tao Chen, Tinevimbo Shiri, Shabbar Jaffar, Thomas S. Harrison, Joseph N. Jarvis, Louis Niessen

London School of Hygiene and Tropical Medicine
Botswana-Harvard AIDS Institute Partnership
Makerere University
University of Minnesota Twin Cities
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Kamuzu University of Health Sciences
Imperial College London
University of North Carolina at Chapel Hill
University of Cape Town
Mbarara University of Science and Technology
University of Botswana
University of Zimbabwe
Institut Pasteur Paris
Université Paris Cité
City St George's, University of London
University of Liverpool
Health Economics and Outcomes Research Ltd
St George's University Hospitals NHS Foundation Trust
University of Exeter
Johns Hopkins University

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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.

Original language	English
Pages (from-to)	e1845-e1854
Journal	The Lancet Global Health
Volume	10
Issue number	12
Early online date	16 Nov 2022
DOIs	https://doi.org/10.1016/s2214-109x(22)00450-8
Publication status	Published - 1 Dec 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

The AMBITION Study Group, Lawrence, D. S., Muthoga, C., Meya, D. B., Tugume, L., Williams, D., Rajasingham, R., Boulware, D. R., Mwandumba, H., Moyo, M., Dziwani, E. N., Maheswaran, H., Kanyama, C., Hosseinipour, M. C., Chawinga, C., Meintjes, G., Schutz, C., Comins, K., Bango, F., ... Niessen, L. (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. The Lancet Global Health, 10(12), e1845-e1854. https://doi.org/10.1016/s2214-109x(22)00450-8

@article{448d8193db8140588bc7631109c0ecbf,

title = "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.",

abstract = "BackgroundHIV-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.MethodsThe 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.FindingsThe 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.InterpretationThe 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.",

author = "\{The AMBITION Study Group\} and Lawrence, \{David S.\} and Charles Muthoga and Meya, \{David B.\} and Lillian Tugume and Darlisha Williams and Radha Rajasingham and Boulware, \{David R.\} and Henry Mwandumba and Melanie Moyo and Dziwani, \{Eltas N.\} and Hendramoorthy Maheswaran and Cecilia Kanyama and Hosseinipour, \{Mina C.\} and Chimwemwe Chawinga and Graeme Meintjes and Charlotte Schutz and Kyla Comins and Funeka Bango and Conrad Muzoora and Samuel Jjunju and Edwin Nuwagira and Mosepele Mosepele and Tshepo Leeme and Ndhlovu, \{Chiratidzo E.\} and Admire Hlupeni and Shepherd Shamu and Timoth{\'e}e Boyer-Chammard and Molloy, \{S{\'i}le F.\} and Nabila Youssouf and Tao Chen and Tinevimbo Shiri and Shabbar Jaffar and Harrison, \{Thomas S.\} and Jarvis, \{Joseph N.\} and Louis Niessen and Jack Goodall and Kwana Lechiile and Norah Mawoko and Tshepiso Mbangiwa and James Milburn and Refilwe Mmipi and Ponego Ponatshego and Ikanyang Rulaganyang and Kaelo Seatla and Keatlaretse Siamisang and Nametso Tlhako and Katlego Tsholo and Samantha April and Abulele Bekiswa and Linda Boloko",

year = "2022",

month = dec,

day = "1",

doi = "10.1016/s2214-109x(22)00450-8",

language = "English",

volume = "10",

pages = "e1845--e1854",

journal = "The Lancet Global Health",

issn = "2572-116X",

publisher = "Elsevier Ltd",

number = "12",

}

The AMBITION Study Group, Lawrence, DS, Muthoga, C, Meya, DB, Tugume, L, Williams, D, Rajasingham, R, Boulware, DR, Mwandumba, H, Moyo, M, Dziwani, EN, Maheswaran, H, Kanyama, C, Hosseinipour, MC, Chawinga, C, Meintjes, G, Schutz, C, Comins, K, Bango, F, Muzoora, C, Jjunju, S, Nuwagira, E, Mosepele, M, Leeme, T, Ndhlovu, CE, Hlupeni, A, Shamu, S, Boyer-Chammard, T, Molloy, SF, Youssouf, N, Chen, T, Shiri, T, Jaffar, S, Harrison, TS, Jarvis, JN & Niessen, L 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.', The Lancet Global Health, vol. 10, no. 12, pp. e1845-e1854. https://doi.org/10.1016/s2214-109x(22)00450-8

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. / The AMBITION Study Group; Lawrence, David S.; Muthoga, Charles et al.
In: The Lancet Global Health, Vol. 10, No. 12, 01.12.2022, p. e1845-e1854.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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.

AU - The AMBITION Study Group

AU - Lawrence, David S.

AU - Muthoga, Charles

AU - Meya, David B.

AU - Tugume, Lillian

AU - Williams, Darlisha

AU - Rajasingham, Radha

AU - Boulware, David R.

AU - Mwandumba, Henry

AU - Moyo, Melanie

AU - Dziwani, Eltas N.

AU - Maheswaran, Hendramoorthy

AU - Kanyama, Cecilia

AU - Hosseinipour, Mina C.

AU - Chawinga, Chimwemwe

AU - Meintjes, Graeme

AU - Schutz, Charlotte

AU - Comins, Kyla

AU - Bango, Funeka

AU - Muzoora, Conrad

AU - Jjunju, Samuel

AU - Nuwagira, Edwin

AU - Mosepele, Mosepele

AU - Leeme, Tshepo

AU - Ndhlovu, Chiratidzo E.

AU - Hlupeni, Admire

AU - Shamu, Shepherd

AU - Boyer-Chammard, Timothée

AU - Molloy, Síle F.

AU - Youssouf, Nabila

AU - Chen, Tao

AU - Shiri, Tinevimbo

AU - Jaffar, Shabbar

AU - Harrison, Thomas S.

AU - Jarvis, Joseph N.

AU - Niessen, Louis

AU - Goodall, Jack

AU - Lechiile, Kwana

AU - Mawoko, Norah

AU - Mbangiwa, Tshepiso

AU - Milburn, James

AU - Mmipi, Refilwe

AU - Ponatshego, Ponego

AU - Rulaganyang, Ikanyang

AU - Seatla, Kaelo

AU - Siamisang, Keatlaretse

AU - Tlhako, Nametso

AU - Tsholo, Katlego

AU - April, Samantha

AU - Bekiswa, Abulele

AU - Boloko, Linda

PY - 2022/12/1

Y1 - 2022/12/1

N2 - BackgroundHIV-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.MethodsThe 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.FindingsThe 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.InterpretationThe 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.

AB - BackgroundHIV-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.MethodsThe 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.FindingsThe 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.InterpretationThe 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.

U2 - 10.1016/s2214-109x(22)00450-8

DO - 10.1016/s2214-109x(22)00450-8

M3 - Article

SN - 2572-116X

VL - 10

SP - e1845-e1854

JO - The Lancet Global Health

JF - The Lancet Global Health

IS - 12

ER -

The AMBITION Study Group, Lawrence DS, Muthoga C, Meya DB, Tugume L, Williams D et al. 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. The Lancet Global Health. 2022 Dec 1;10(12):e1845-e1854. Epub 2022 Nov 16. doi: 10.1016/s2214-109x(22)00450-8

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.

Abstract

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