TY - JOUR
T1 - HIV-Associated cryptococcal meningitis occurring at relatively higher CD4 counts
AU - Tugume, Lillian
AU - Rhein, Joshua
AU - Hullsiek, Kathy Huppler
AU - Mpoza, Edward
AU - Kiggundu, Reuben
AU - Ssebambulidde, Kenneth
AU - Schutz, Charlotte
AU - Taseera, Kabanda
AU - Williams, Darlisha A.
AU - Abassi, Mahsa
AU - Muzoora, Conrad
AU - Musubire, Abdu K.
AU - Meintjes, Graeme
AU - Meya, David B.
AU - Boulware, David R.
AU - Nabeta, Henry W.
AU - Ndyetukira, Jane Francis
AU - Ahimbisibwe, Cynthia
AU - Kugonza, Florence
AU - Namuju, Carolyne
AU - Sadiq, Alisat
AU - Namudde, Alice
AU - Mwesigye, James
AU - Kandole, Tadeo Kiiza
AU - Kwizera, Richard
AU - Kirumira, Paul
AU - Okirwoth, Michael
AU - Akampurira, Andrew
AU - Luggya, Tony
AU - Kaboggoza, Julian
AU - Laker, Eva
AU - Atwine, Leo
AU - Muganzi, Davis
AU - Evans, Emily E.
AU - Bridge, Sarah C.
AU - Velamakanni, Sruti S.
AU - Rajasingham, Radha
AU - Pastick, Katelyn
AU - Stadelman, Anna
AU - Flynn, Andrew
AU - Fujita, A. Wendy
AU - Mukaremera, Liliane
AU - Lofgren, Sarah M.
AU - Morawski, Bozena M.
AU - Bangdiwala, Ananta
AU - Nielsen, Kirsten
AU - Bohjanen, Paul R.
AU - Kambugu, Andrew
N1 - Publisher Copyright:
© 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2019/2/23
Y1 - 2019/2/23
N2 - 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.
AB - 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.
KW - AIDS
KW - CD4 T cells
KW - CSF biomarkers
KW - HIV
KW - cryptococcal meningitis
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U2 - 10.1093/infdis/jiy602
DO - 10.1093/infdis/jiy602
M3 - Article
C2 - 30325463
AN - SCOPUS:85059299272
SN - 0022-1899
VL - 219
SP - 877
EP - 883
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -