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Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: a nationwide cohort study

Authors Touma M, Rasmussen LD, Martin-Iguacel R, Engsig FN, Stærke NB, Stærkind M, Obel N, Ahlström MG

Received 21 February 2017

Accepted for publication 3 May 2017

Published 21 July 2017 Volume 2017:9 Pages 385—392


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Irene Petersen

Madeleine Touma,1 Line D Rasmussen,2 Raquel Martin-Iguacel,2 Frederik Neess Engsig,3 Nina Breinholt Stærke,4 Mette Stærkind,5 Niels Obel,1 Magnus Glindvad Ahlström1

1Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2Department of Infectious Diseases, Odense University Hospital, Odense, 3Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, 4Department of Infectious Diseases, Aarhus University Hospital, Aarhus, 5Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark

Background: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era.
Methods: A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995–2014 was included in this study.
Results: Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995–1996, 1997–1999, and 2000–2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05–0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00–4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10–50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity.
Conclusion: The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.

Keywords: cryptococcal meningitis, highly active antiretroviral therapy, HIV

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