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Clin Infect Dis. 2016 Mar 1;62(5):581-587. doi: 10.1093/cid/civ936. Epub 2015 Nov 12.

Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study.

Author information

1
Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
2
Institute for Infection and Immunity, St. George's University of London, United Kingdom.
3
Department of Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
4
Botswana-Upenn Partnership, Gaborone.
5
Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
6
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
7
School of Public Health and Family Medicine and Institute of Infectious Disease and Molecular Medicine, University of Cape Town.
8
Health Impact Assessment Directorate, Department of Health, Provincial Government of the Western Cape.
9
National Institute for Communicable Diseases, a Division of the National Health Laboratory Service-Centre for Opportunistic, Tropical and Hospital Infections.
10
Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

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.

KEYWORDS:

HIV; antiretroviral therapy; cryptococcal antigen; cryptococcal meningitis; screening

PMID:
26565007
PMCID:
PMC4741358
DOI:
10.1093/cid/civ936
[Indexed for MEDLINE]
Free PMC Article

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