Screening for cryptococcal antigen (CrAg) among those with advanced HIV disease and treating asymptomatic CrAg+ with fluconazole is lifesaving. However, fluconazole monotherapy still results in 25% mortality.1 Enhanced preemptive treatment options are being evaluated to prevent cryptococcal meningitis. Single dose Ambisome (at 10mg/kg) plus fluconazole is being prospectively evaluated for preemptive treatment in asymptomatic CrAg+. We sought to explore the threshold of efficacy and cost that would improve on current standard of care therapy in Uganda and South Africa, representing a low income setting and a middle income setting respectively. The current price of Ambisome in South Africa is $165 per vial. The anticipated discounted price for treatment of cryptococcal meningitis in resource-limited settings is $16.25 per vial.
We used a decision analytic model to evaluate CrAg screening and treatment outcomes in Uganda for those with a CD4<100 cells/µL. Costs were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were taken from large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa.2 CrAg-positive persons could be: a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or b) symptomatic with meningitis with hospitalization. We varied parameters to approximate South African CrAg prevalence and hospitalization costs.
At a discounted price of $16.25 per vial, assuming 95% efficacy, Ambisome would be cost-saving to the Ugandan national healthcare system, primarily in meningitis hospitalization costs averted. At the same cost, but assuming 85% efficacy, the cost is $195 to save one life. In South Africa, at the current price of $165 per vial, if assumed to have 95% efficacy, the cost is $3090 to prevent one death from cryptococcal meningitis. At the same price, but assuming 85% efficacy, it would cost $4817 to prevent one death (Figure). If Ambisome was priced at $72 per vial or less, this would be cost saving if efficacy is 85% or more. At a discounted price of $16.25 per vial and 85% efficacy, the health care system would save $2949 for every death averted from cryptococcal meningitis.
Single dose Ambisome for asymptomatic cryptococcal infection given at 10mg/kg once in conjunction with fluconazole has potential to save lives and save costs, if proven effective.