title: Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings.
abstract: 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 $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 < or = 100 cells/microL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.
authors.affiliation: Infectious Disease Institute, Makerere University, Mulago Hospital Complex, Kampala, Uganda. david.meya@gmail.com
authors.forename: David B
authors.initials: DB
authors.lastname: Meya
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
authors.forename: Barbara
authors.initials: B
authors.lastname: Castelnuovo
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Cook
authors.forename: Ali M
authors.initials: AM
authors.lastname: Elbireer
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Paul R
authors.initials: PR
authors.lastname: Bohjanen
authors.forename: David R
authors.initials: DR
authors.lastname: Boulware
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage; D000946:Antigens, Fungal / Q000097:blood*; D018791:CD4 Lymphocyte Count; D018890:Chemoprevention / Q000379:methods; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D003453:Cryptococcosis / Q000175:diagnosis* / Q000517:prevention & control; D003454:Cryptococcus / Q000302:isolation & purification*; D003906:Developing Countries; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000191:economics* / Q000379:methods; D009172:Mycology / Q000191:economics* / Q000379:methods; D014454:Uganda
chemical_list: D000935:Antifungal Agents; D000946:Antigens, Fungal; D015725:Fluconazole