Cost-effectiveness analysis of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa

The 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. A decision analytic cost-effectiveness and cost 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 five treatment arms: standard of care; 2-week course amphotericin B/fluconazole (2wk AmBd/Flu), 2-week course amphotericin B/flucytosine (2wk AmBd/5FC), short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC), oral course; 2-week oral fluconazole/flucytosine (oral), and 1-week course amphotericin B/fluconazole (1wk AmBd/Flu). A sensitivity analysis was conducted on key variables. The highest total treatment costs are in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, the 1-week AmBd/5FC, then standard of care with the lowest cost in the 1-week AmBd/Flu arm. Compared to the lowest cost option, the 1-week flucytosine course is most cost-effective at USD119/QALY. The cost impact analysis shows that the 1-week flucytosine course has an incremental cost of just over USD293 per patient per year compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to life expectancy and hospital costs, particularly infusion costs and length of stay. The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective when it is used as a 1-week AmBd/5FC regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine. The World Health Organization (WHO) has updated its guideline to recommend a combination induction phase of one week of intravenous amphotericin B and oral 5-flucytosine or, as an alternative, two weeks of oral flucytosine and fluconazole. The Southern African HIV Clinicians Society recently released an updated guideline for the management of cryptococcal disease in PLHIV, which includes a recommendation for 1-week amphotericin B and flucytosine as induction therapy. The study population of interest in this analysis were HIV-infected adults presenting with cryptococcal meningitis to a public health facility in South Africa. In general, these patients are treated at either a secondary (district or regional hospital) or tertiary and quaternary (specialist or teaching hospital) facility. Patients are usually treated in a general ward rather than an ICU or high-care setting. The study perspective was that of a provider, in this instance the South African Government, and therefore costs and outcomes were considered from the viewpoint of the public sector.