Abstract
BackgroundMortality 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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.
Highlights
MethodsThe effectiveness and costs of FLU+5FC were taken from Advancing Cryptococcal Meningitis Treatment for Africa (ACTA), which included a costing analysis at the Zambian site
Mortality from cryptococcal meningitis remains very high in Africa
Many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain
Summary
The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. ACTA was a large, open-label, Phase III, randomized, noninferiority, multicenter trial, in which 721 patients with human immunodeficiency virus–associated cryptococcal meningitis from centers in Malawi, Zambia, Tanzania, and Cameroon were randomized to 3 strategies: 2 weeks of oral FLU+5FC, 1 week of AmB, or the standard 2 weeks of AmB. Those in the AmB arms were further randomized to 5FC or FLU, in a 1:1 ratio, as the partner drug given with AmB. The inflation change for 2015 to 2018 was modest, at 5.9%
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