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 journalArticle

10 Scopus citations

Abstract

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
Volume219
Issue number6
DOIs
StatePublished - Feb 23 2019

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Keywords

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

PubMed: MeSH publication types

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

Cite this

Tugume, L., Rhein, J., Hullsiek, K. H., Mpoza, E., Kiggundu, R., Ssebambulidde, K., Schutz, C., Taseera, K., Williams, D. A., Abassi, M., Muzoora, C., Musubire, A. K., Meintjes, G., Meya, D. B., Boulware, D. R., Nabeta, H. W., Ndyetukira, J. F., Ahimbisibwe, C., Kugonza, F., ... Kambugu, A. (2019). HIV-Associated cryptococcal meningitis occurring at relatively higher CD4 counts. Journal of Infectious Diseases, 219(6), 877-883. https://doi.org/10.1093/infdis/jiy602