Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 16;76(12):2116-2125.
doi: 10.1093/cid/ciad076.

Cryptococcal Meningitis and Clinical Outcomes in Persons With Human Immunodeficiency Virus: A Global View

Anna K Person  1 , Brenda Crabtree-Ramirez  2 , Ahra Kim  3 , Valdiléa Veloso  4 , Fernanda Maruri  1 , Gilles Wandeler  5 , Matthew Fox  6 , Richard Moore  7 , M John Gill  8 , Darma Imran  9 , Kinh Van Nguyen  10 , Elizabeth Nalitya  11 , Winnie Muyindike  12 , Bryan E Shepherd  3 , Catherine C McGowan  1
Affiliations

Cryptococcal Meningitis and Clinical Outcomes in Persons With Human Immunodeficiency Virus: A Global View

Anna K Person et al. Clin Infect Dis. .

Abstract

Background: Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV; PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally.

Methods: In this retrospective cohort study, we investigated CM incidence and all-cause mortality in PWH in the International Epidemiology Databases to Evaluate AIDS cohort from 1996 to 2017. We estimated incidence using quasi-Poisson models adjusted for sex, age, calendar year, CD4 cell count (CD4), and antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities.

Results: Among 518 852 PWH, there were 3857 cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. In total, 2478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (hazard [HR], 1.31 for 50 vs 35 years), lower CD4 (HR, 1.15 for 200 vs 350 cells/mm3), and earlier year of CM diagnosis (HR, 0.51 for 2015 vs 2000) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine.

Conclusions: Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.

Keywords: AIDS; HIV; cryptococcal meningitis; global health.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. M. J. G. reports an NIH subgrant from JSPHU to the University of Calgary and honoraria for participation as an ad hoc member of HIV Canadian advisory boards to Merck, ViiV Healthcare, and Gilead. G. W. reports unrestricted research grants from Roche Diagnostics and Gilead Sciences and honoraria for advisory board participation and/or travel grants from MSD, Gilead Sciences, and ViiV Healthcare, all paid to their institution. A. K. P. reports participation on the HIV Medicine Association Board of Directors and receipt of support for attending meetings and/or travel including Vanderbilt continuing medical education funds. C. C. M. reports support for attending meetings and/or travel from NIH paid to their institution. All other authors report no potential conflicts. 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.

Figures

Figure 1.
Figure 1.
Incidence of cryptococcal meningitis (CM) diagnosis. A, Unadjusted incidence of CM diagnosis per 1000-person years (95% CIs) according to region and overall. B, Incidence (95% CI) of CM diagnosis across all sites according to calendar year; dashed line represents crude estimates for that year, dark line represents model-based estimates smoothing across calendar years. Abbreviation: CI, confidence interval.
Figure 2.
Figure 2.
Estimated IRR (95% CI) of risk factors for cryptococcal meningitis combined across all regions, in adjusted analyses. Abbreviations: ART, antiretroviral therapy; CI, confidence interval; IRR, incidence rate ratio.
Figure 3.
Figure 3.
All-cause mortality after diagnosis of cryptococcal meningitis, overall and stratified by whether diagnosis was before or after ART initiation. A, Estimated probabilities based on Kaplan–Meier curves. B, Estimated probability of death or loss to follow-up based on Kaplan–Meier curves. C, Estimated cumulative incidence of death treating loss to follow-up as a competing event. Abbreviation: ART, antiretroviral therapy.
Figure 4.
Figure 4.
Estimated HRs (95% CIs) of risk factors for all-cause mortality after diagnosis of CM combined across regions, in adjusted analyses. Abbreviations: ART, antiretroviral therapy; CI, confidence interval; CM, cryptococcal meningitis; HR, hazard ratio.
See this image and copyright information in PMC

References

    1. Molloy SF, Kanyama C, Heyderman RS, et al. . Antifungal combinations for treatment of cryptococcal meningitis in Africa. N Engl J Med 2018; 378:1004–17. - PubMed
    1. Lawrence DS, Boyer-Chammard T, Jarvis JN. Emerging concepts in HIV-associated cryptococcal meningitis. Curr Opin Infect Dis 2019; 32:16–23. - PubMed
    1. Beardsley J, Wolbers M, Kibengo FM, et al. . Adjunctive dexamethasone in HIV-associated cryptococcal meningitis. N Engl J Med 2016; 374:542–54. - PMC - PubMed
    1. Rajasingham R, Govender NP, Jordan A, et al. . The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis 2022; 22:1748–55. - PMC - PubMed
    1. Rajasingham R, Smith RM, Park BJ, et al. . Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17:873–81. - PMC - PubMed

Publication types

MeSH terms