Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis

Tinevimbo Shiri, Angela Loyse, Lawrence Mwenge, Tao Chen, Shabir Lakhi, Duncan Chanda, Peter Mwaba, Síle F. Molloy, Robert S. Heyderman, Cecilia Kanyama, Mina C. Hosseinipour, Charles Kouanfack, Elvis Temfack, Sayoki Mfinanga, Sokoine Kivuyo, Adrienne K. Chan, Joseph N. Jarvis, Olivier Lortholary, Shabbar Jaffar, Louis W. NiessenThomas S. Harrison

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. METHODS: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. RESULTS: The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. CONCLUSIONS: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.

Original languageEnglish (US)
Pages (from-to)26-29
Number of pages4
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume70
Issue number1
DOIs
StatePublished - Jan 1 2020

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Cryptococcal Meningitis
Flucytosine
Fluconazole
Cost-Benefit Analysis
Therapeutics
Confidence Intervals
Costs and Cost Analysis
Drug Costs
Mortality
Drug Monitoring

Keywords

  • cost-effectiveness
  • cryptococcal meningitis
  • fluconazole
  • flucytosine
  • treatment

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa : A Multicountry Cost-effectiveness Analysis. / Shiri, Tinevimbo; Loyse, Angela; Mwenge, Lawrence; Chen, Tao; Lakhi, Shabir; Chanda, Duncan; Mwaba, Peter; Molloy, Síle F.; Heyderman, Robert S.; Kanyama, Cecilia; Hosseinipour, Mina C.; Kouanfack, Charles; Temfack, Elvis; Mfinanga, Sayoki; Kivuyo, Sokoine; Chan, Adrienne K.; Jarvis, Joseph N.; Lortholary, Olivier; Jaffar, Shabbar; Niessen, Louis W.; Harrison, Thomas S.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 70, No. 1, 01.01.2020, p. 26-29.

Research output: Contribution to journalArticle

Shiri, T, Loyse, A, Mwenge, L, Chen, T, Lakhi, S, Chanda, D, Mwaba, P, Molloy, SF, Heyderman, RS, Kanyama, C, Hosseinipour, MC, Kouanfack, C, Temfack, E, Mfinanga, S, Kivuyo, S, Chan, AK, Jarvis, JN, Lortholary, O, Jaffar, S, Niessen, LW & Harrison, TS 2020, 'Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 70, no. 1, pp. 26-29. https://doi.org/10.1093/cid/ciz163
Shiri, Tinevimbo ; Loyse, Angela ; Mwenge, Lawrence ; Chen, Tao ; Lakhi, Shabir ; Chanda, Duncan ; Mwaba, Peter ; Molloy, Síle F. ; Heyderman, Robert S. ; Kanyama, Cecilia ; Hosseinipour, Mina C. ; Kouanfack, Charles ; Temfack, Elvis ; Mfinanga, Sayoki ; Kivuyo, Sokoine ; Chan, Adrienne K. ; Jarvis, Joseph N. ; Lortholary, Olivier ; Jaffar, Shabbar ; Niessen, Louis W. ; Harrison, Thomas S. / Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa : A Multicountry Cost-effectiveness Analysis. In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 ; Vol. 70, No. 1. pp. 26-29.
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abstract = "BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. METHODS: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. RESULTS: The mean costs per patient were US $847 (95{\%} confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95{\%} CI $557-709) for FLU. The 10-week mortality rate was 35.1{\%} (95{\%} CI 28.9-41.7{\%}) with FLU+5FC and 53.8{\%} (95{\%} CI 43.1-64.1{\%}) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95{\%} CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. CONCLUSIONS: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.",
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TY - JOUR

T1 - Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa

T2 - A Multicountry Cost-effectiveness Analysis

AU - Shiri, Tinevimbo

AU - Loyse, Angela

AU - Mwenge, Lawrence

AU - Chen, Tao

AU - Lakhi, Shabir

AU - Chanda, Duncan

AU - Mwaba, Peter

AU - Molloy, Síle F.

AU - Heyderman, Robert S.

AU - Kanyama, Cecilia

AU - Hosseinipour, Mina C.

AU - Kouanfack, Charles

AU - Temfack, Elvis

AU - Mfinanga, Sayoki

AU - Kivuyo, Sokoine

AU - Chan, Adrienne K.

AU - Jarvis, Joseph N.

AU - Lortholary, Olivier

AU - Jaffar, Shabbar

AU - Niessen, Louis W.

AU - Harrison, Thomas S.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. METHODS: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. RESULTS: The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. CONCLUSIONS: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.

AB - BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. METHODS: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. RESULTS: The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. CONCLUSIONS: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.

KW - cost-effectiveness

KW - cryptococcal meningitis

KW - fluconazole

KW - flucytosine

KW - treatment

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