title: Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study.
abstract: BACKGROUND
  Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited.
  
  
  METHODS
  CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year.
  
  
  RESULTS
  A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg-positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients.
  
  
  CONCLUSIONS
  CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease.
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.|Institute for Infection and Immunity, St. George's University of London, United Kingdom.|Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Nicky
authors.initials: N
authors.lastname: Longley
authors.affiliation: Botswana-Upenn Partnership, Gaborone.|Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.|Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Joseph Nicholas
authors.initials: JN
authors.lastname: Jarvis
authors.affiliation: Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: School of Public Health and Family Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town.|Health Impact Assessment Directorate, Department of Health, Provincial Government of the Western Cape.
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Anna
authors.initials: A
authors.lastname: Cross
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Nicola
authors.initials: N
authors.lastname: Kelly
authors.affiliation: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service-Centre for Opportunistic, Tropical and Hospital Infections.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nelesh P
authors.initials: NP
authors.lastname: Govender
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.|Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.|Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.affiliation: Institute for Infection and Immunity, St. George's University of London, United Kingdom.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis* / Q000401:mortality / Q000517:prevention & control; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000032:analysis* / Q000097:blood / Q000652:urine; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008403:Mass Screening; D016919:Meningitis, Cryptococcal / Q000150:complications / Q000175:diagnosis* / Q000517:prevention & control; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D000935:Antifungal Agents; D000946:Antigens, Fungal
keywords: HIV; antiretroviral therapy; cryptococcal antigen; cryptococcal meningitis; screening