Abstract
Background Cryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135 000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa. Methods A decision analytic cost-effectiveness and budget impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered four treatment arms: (a) standard of care; 2-week course of amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course of amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) and (d) oral course; 2-week oral fluconazole/flucytosine (oral). A sensitivity analysis was conducted on key variables. Results The highest total treatment costs were in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, then the 1-week AmBd/5FC with the lowest cost in the standard of care arm. Compared to standard of care the 1-week flucytosine course is most cost-effective at USD31/QALY, followed by the oral 2-week course at USD155/QALY and the 2-week flucytosine course at USD568/QALY. The budget impact analysis shows that the 1-week course has the lowest incremental cost, followed by the oral course and then the 2-week flucytosine course compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to the price of flucytosine and hospital costs, particularly length of stay. Conclusions The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective regardless of whether it is used as a 1-week, 2-week or oral regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.
Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa
