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Addition of flucytosine to fluconazole for the treatment of cryptococcal meningitis in Africa: a multi-country cost-effectiveness analysis.

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Shiri, Tinevimbo ORCID: https://orcid.org/0000-0002-9092-3268, Loyse, Angela, Mwenge, Lawrence, Chen, Tao ORCID: https://orcid.org/0000-0002-5489-6450, Lakhi, Shabir, Chanda, Duncan, Mwaba, Peter, Molloy, Síle F, Heyderman, Robert, 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 ORCID: https://orcid.org/0000-0002-8639-5191 and Harrison, Thomas (2019) 'Addition of flucytosine to fluconazole for the treatment of cryptococcal meningitis in Africa: a multi-country cost-effectiveness analysis.'. Clinical Infectious Diseases. (In Press)

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Abstract

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.

Item Type: Article
Subjects: W General Medicine. Health Professions > W 74 Medical economics. Health care costs
QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 252 Antifungal agents. Antifungal antibiotics
WA Public Health > WA 30 Socioeconomic factors in public health (General)
WL Nervous System > WL 200 Meninges. Blood-brain barrier
WL Nervous System > WL 300 General works (Include works on brain alone)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/ciz163
Depositing User: Stacy Murtagh
Date Deposited: 04 Mar 2019 15:38
Last Modified: 14 Jun 2019 09:02
URI: https://archive.lstmed.ac.uk/id/eprint/10306

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