HIV-Associated cryptococcal meningitis occurring at relatively higher CD4 counts

Lillian Tugume, Joshua Rhein, Kathy Huppler Hullsiek, Edward Mpoza, Reuben Kiggundu, Kenneth Ssebambulidde, Charlotte Schutz, Kabanda Taseera, Darlisha A. Williams, Mahsa Abassi, Conrad Muzoora, Abdu K. Musubire, Graeme Meintjes, David B. Meya, David R. Boulware, Henry W. Nabeta, Jane Francis Ndyetukira, Cynthia Ahimbisibwe, Florence Kugonza, Carolyne NamujuAlisat Sadiq, Alice Namudde, James Mwesigye, Tadeo Kiiza Kandole, Richard Kwizera, Paul Kirumira, Michael Okirwoth, Andrew Akampurira, Tony Luggya, Julian Kaboggoza, Eva Laker, Leo Atwine, Davis Muganzi, Emily E. Evans, Sarah C. Bridge, Sruti S. Velamakanni, Radha Rajasingham, Katelyn Pastick, Anna Stadelman, Andrew Flynn, A. Wendy Fujita, Liliane Mukaremera, Sarah M. Lofgren, Bozena M. Morawski, Ananta Bangdiwala, Kirsten Nielsen, Paul R. Bohjanen, Andrew Kambugu

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


BACKGROUND: Cryptococcal meningitis can occur in persons with less-apparent immunosuppression. We evaluated clinical characteristics and outcomes of persons with HIV-related Cryptococcus presenting with higher CD4 counts.

METHODS: We enrolled 736 participants from 2 prospective cohorts in Uganda and South Africa from November 2010 to May 2017. We compared participants with CD4 <50, 50-99, or ≥100 cells/μL by clinical characteristics, cerebrospinal fluid (CSF) parameters, and 18-week survival.

RESULTS: Among first episode of cryptococcosis, 9% presented with CD4 ≥100 cells/μL. Participants with CD4 ≥100 cells/μL presented more often with altered mental status (52% vs 39%; P = .03) despite a 10-fold lower initial median CSF fungal burden of 7850 (interquartile range [IQR] 860-65500) versus 79000 (IQR 7400-380000) colony forming units/mL (P < .001). Participants with CD4 ≥100 cells/μL had higher median CSF levels of interferon-gamma, interleukin (IL)-6, IL-8, and IL-13, and lower monocyte chemokine, CCL2 (P < .01 for each). Death within 18 weeks occurred in 47% with CD4 <50, 35% with CD4 50-99, and 40% with CD4 ≥100 cells/μL (P = .04).

CONCLUSION: HIV-infected individuals developing cryptococcal meningitis with CD4 ≥100 cells/μL presented more frequently with altered mental status despite having 10-fold lower fungal burden and with greater Th2 (IL-13) immune response. Higher CD4 count was protective despite an increased propensity for immune-mediated damage, consistent with damage-response framework.


Original languageEnglish (US)
Pages (from-to)877-883
Number of pages7
JournalJournal of Infectious Diseases
Issue number6
StatePublished - Feb 23 2019

Bibliographical note

Funding Information:
Financial support. This work was supported by the National Institute of Neurologic Diseases and Stroke (grant number R01NS086312); the Fogarty International Center (grant numbers K01TW010268, R25TW009345); the National Institute of Allergy and Infectious Diseases (grant numbers T32AI055433, U01AI089244); the Wellcome Trust (grant number 098316 to G. M.); and the Department of Science and Technology and National Research Foundation of South Africa Research Chairs Initiative (grant number 64787) and incentive funding (grant number UID: 85858). Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Publisher Copyright:
© 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.


  • AIDS
  • CD4 T cells
  • CSF biomarkers
  • HIV
  • cryptococcal meningitis

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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