David B. Meya

Cost-Effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-Infected Persons with a CD4+ Cell Count ≤100 Cells/μL Who Start HIV therapy in resource-limited settings

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 > or = 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 < or = 100 cells/microL 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 < or = 100 cells/microL 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

Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study

190 (95% CI,

Paucity of Initial Cerebrospinal Fluid Inflammation in Cryptococcal Meningitis is associated with subsequent Immune Reconstitution Inflammatory Syndrome

132-

Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care.

287). The number needed to test and treat to save 1 life is 15.9 (95% CI, 11.1-24.0) at costs of

Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study

266 (95% CI,

Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis

185-

Cryptococcus neoformans Ex Vivo Capsule Size Is Associated With Intracranial Pressure and Host Immune Response in HIV-associated Cryptococcal Meningitis

402). The cost per disability-adjusted life year saved is

Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda

21 (95% CI,

Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis

15-

Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda

32). CONCLUSIONS Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4(+) cell count < or = 100 cells/microL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.