title: Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.
abstract: BACKGROUND
  In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies.
  
  
  METHODS
  We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions.
  
  
  RESULTS
  In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment).
  
  
  CONCLUSIONS
  In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.
authors.affiliation: Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Bruce A
authors.identifier: http://orcid.org/0000-0002-9322-2387
authors.initials: BA
authors.lastname: Larson
authors.affiliation: Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Rockers
authors.affiliation: Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, United States of America.|Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Rachael
authors.initials: R
authors.lastname: Bonawitz
authors.affiliation: National Institute for Communicable Diseases - Centre for Opportunistic, Tropical and Hospital Infections, Johannesburg, South Africa.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sriruttan
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Glencross
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Naseem
authors.initials: N
authors.lastname: Cassim
authors.affiliation: National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Lindi M
authors.initials: LM
authors.lastname: Coetzee
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Greene
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Tom M
authors.initials: TM
authors.lastname: Chiller
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Vallabhaneni
authors.affiliation: Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Health Economics and Epidemiology Office, Wits Health Consortium, Johannesburg, South Africa.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Long
authors.affiliation: Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Health Economics and Epidemiology Office, Wits Health Consortium, Johannesburg, South Africa.
authors.forename: Craig
authors.initials: C
authors.lastname: van Rensburg
authors.affiliation: National Institute for Communicable Diseases - Centre for Opportunistic, Tropical and Hospital Infections, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nelesh P
authors.initials: NP
authors.lastname: Govender
mesh_terms: D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000191:economics; D000946:Antigens, Fungal / Q000097:blood / Q000276:immunology; D018791:CD4 Lymphocyte Count; D003365:Costs and Cost Analysis; D003453:Cryptococcosis / Q000097:blood / Q000191:economics / Q000453:epidemiology; D003454:Cryptococcus / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000191:economics / Q000453:epidemiology; D015497:HIV-1; D006801:Humans; D008297:Male; D008403:Mass Screening; D008954:Models, Biological; D013019:South Africa
chemical_list: D044966:Anti-Retroviral Agents; D000946:Antigens, Fungal