Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons. We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/μL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at $16.25 to $40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted. In South Africa, at $16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost $475, $220, or $136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at $24 per vial cost. Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. Lay Summary: We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings.
Bibliographical noteFunding Information:
Acknowledgments RR is supported by the National Institute of Allergy and Infectious diseases (K23AI138851). BL supported by grant from CDC foundation. Gilead Sciences Inc. has provided funding to the Meningitis foundation, with which RR, DM, and DB are affiliated. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies. The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc.
© 2022 The Author(s). Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
- Amphotericin B
- Antifungal Agents/therapeutic use
- Antigens, Fungal
- CD4 Lymphocyte Count/veterinary
- Cost-Benefit Analysis
- Developing Countries
- HIV Infections/drug therapy
- Meningitis, Cryptococcal/drug therapy
- Prospective Studies
PubMed: MeSH publication types
- Journal Article