Background. Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Subclinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART).We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with subclinical cryptococcosis and the efficacy of preemptive fluconazole therapy. Methods. There were 609 ART-naive adults with AIDS who started ART in Kampala, Uganda, and who had a serum CRAG prospectively measured during 2004-2006. The number needed to test and treat with a positive CRAG was assessed for ≥30-month outcomes. Results. In the overall cohort, 50 persons (8.2%) were serum CRAG positive when starting ART. Of 295 people with a CD4 + cell count ≤100 cells/mL and without prior CM, 26 (8.8%; 95% confidence interval [CI], 5.8%- 12.6%) were CRAG positive, of whom 21 were promptly treated with fluconazole (200-400 mg) for 2-4 weeks. Clinical CM developed in 3 fluconazole-treated persons, and 30-month survival was 71% (95% CI, 48%-89%). In the 5 CRAG-positive persons with a CD4+ cell count ≤100 cells/mL treated with ART but not fluconazole, all died within 2 months of ART initiation. The number needed to test and treat with CRAG screening and fluconazole to prevent 1 CM case is 11.3 (95% CI, 7.9-17.1) at costs of $190 (95% CI, $132-$287). The number needed to test and treat to save 1 life is 15.9 (95% CI, 11.1-24.0) at costs of $266 (95% CI, $185-$402). The cost per disability-adjusted life year saved is $21 (95% CI, $15-$32). Conclusions. Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4+ cell count ≤100 cells/mL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.
Bibliographical noteFunding Information:
Financial support. The Infectious Disease Institute is supported in part by a philanthropic grant from Pfizer pharmaceuticals (to B.C., A.K., and M.K.), and this research was supported by the University of Minnesota Academic Health Center (P.R.B. and D.B.M.) and the National Institutes of Health (grant K23AI073192-01A2 to D.R.B. and grant R34 AI081554 to D.R.B., D.B.M., and P.R.B.). Potential conflicts of interest. All authors: no conflicts.