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

Tinevimbo Shiri (1) , Angela Loyse (2) , Lawrence Mwenge (3) , Tao Chen (1) , Shabir Lakhi (4) , Duncan Chanda (5, 6) , Peter Mwaba (7) , Síle Molloy (2) , Robert S Heyderman (8, 9) , Cecilia Kanyama (10) , Mina Hosseinipour (10, 11) , Charles Kouanfack (12, 13) , Elvis Temfack (14, 15, 16) , Sayoki G Mfinanga (17, 1) , Sokoine Kivuyo (17) , Adrienne Chan (18, 19) , Joseph Jarvis (20, 21) , Olivier Lortholary (22, 15, 16) , Shabbar Jaffar (1) , Louis Niessen (1, 23) , Thomas Harrison (2)

1 LSTM - Liverpool School of Tropical Medicine
2 St George's, University of London
3 Zambart Health Economics Unit Lusaka
4 University Teaching Hospital (UTH), Lusaka,
5 UTH - University Teaching Hospital [Lusaka]
6 Institute for Medical Research and Training, University of Teaching Lusaka
7 Department of Internal Medicine and Directorate of Research and Post-graduate Studies, Lusaka Apex Medical University, Zambia
8 University of Malawi
9 UCL - University College of London [London]
10 UNC Project - University of North Carolina Project-Malawi
11 UNC - University of North Carolina [Chapel Hill]
12 Hôpital Central de Yaoundé [Yaoundé]
13 Université de Dschang
14 Hôpital Général de Douala
15 Mycologie moléculaire - Molecular Mycology
16 CNRMA - Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire
17 NIMR - National Institute for Medical Research - Muhimbili Research Centre
18 Zomba Central Hospital Malawi
19 University of Toronto
20 LSHTM - London School of Hygiene and Tropical Medicine
21 Bostwana Harvard AIDS Institute Partneship Gaborone
22 Centre d'infectiologie Necker-Pasteur [CHU Necker]
23 Johns Hopkins Bloomberg School of Public Health [Baltimore]

BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the ACTA trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2-week amphotericin-based regimens. However, many African settings treat with FLU monotherapy and the cost effectiveness of adding 5FC to FLU is uncertain. METHODS: Effectiveness and costs of FLU+5FC were taken from ACTA, which included costing analysis at the Zambian site. 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 subtraction of 5FC drug and monitoring costs.Cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). 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: Mean costs per patient were US$847 (95%CI:776-927) for FLU+5FC, and US$628 (95%CI:557-709) for FLU. 10 week mortality 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 $US1.30 per 500mg tablet, the ICER of 5FC+FLU versus FLU alone was US$65 (95%CI: 28-208) per life year saved. Reducing 5FC cost to between US$0.80 and US$0.40 per 500mg resulted in an ICER between US$44 and US$28 per life year saved. CONCLUSIONS: 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 HIV-infected persons in Africa.

Keywords: cryptococcal meningitis; treatment; flucytosine; fluconazole; cost-effectiveness

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Mycology

Tinevimbo Shiri, Angela Loyse, Lawrence Mwenge, Tao Chen, Shabir Lakhi, et al.. Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis. Clinical Infectious Diseases, 2019, 2019, pp.ciz163. ⟨10.1093/cid/ciz163⟩. ⟨pasteur-02190935⟩