Cryptococcal antigenemia in immunocompromised human immunodeficiency virus patients in rural Tanzania: A preventable cause of early mortality

Emilio Letang, Matthias C. Müller, Alex J. Ntamatungiro, Namvua Kimera, Diana Faini, Hansjakob Furrer, Manuel Battegay, Marcel Tanner, Christoph Hatz, David R. Boulware, Tracy R. Glass

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Background. Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/μL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods. We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/μL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow- up (LFU) by CRAG status and fluconazole use. Results. Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/μL.Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P < .001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions. Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/μL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/μL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold.

Original languageEnglish (US)
JournalOpen Forum Infectious Diseases
Issue number2
StatePublished - Apr 1 2015

Bibliographical note

Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Societyof America.


  • Cryptococcal antigen
  • Cryptococcal meningitis
  • Diagnosis
  • Mortality
  • Prevention
  • Retention in care
  • Screening
  • Sub-Saharan Africa


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