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. 2019 Feb 23;219(6):877-883.
doi: 10.1093/infdis/jiy602.

HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts

Lillian Tugume  1 , Joshua Rhein  1   2 , Kathy Huppler Hullsiek  2 , Edward Mpoza  1 , Reuben Kiggundu  1 , Kenneth Ssebambulidde  1 , Charlotte Schutz  3 , Kabanda Taseera  4 , Darlisha A Williams  1   2 , Mahsa Abassi  1   2 , Conrad Muzoora  4 , Abdu K Musubire  1   2 , Graeme Meintjes  3 , David B Meya  1   5   2 , David R Boulware  2 ; COAT and ASTRO-CM teams
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HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts

Lillian Tugume et al. J Infect Dis. .

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.

Clinical trial registration: NCT01075152 and NCT01802385.

Keywords: AIDS; CD4 T cells; CSF biomarkers; HIV; cryptococcal meningitis.

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Figures

Figure 1.
Figure 1.
Proportions of deaths (95% confidence interval) by 18 weeks for 4 CD4 groups (CD4 ≤25, 25–50, 51–99, and ≥100 cells/μL).
Figure 2.
Figure 2.
Kaplan-Meier curve for cryptococcal meningitis survival by baseline CD4 group.
See this image and copyright information in PMC

References

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