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

Abstract

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

Acknowledgments

This work was supported by Preben og Anne Simonsens Foundation, NOVO Nordisk Foundation, Rigshospitalet, Copenhagen University, The Danish AIDS Foundation, and The Augustinus Foundation.

Study centers of the Danish HIV Cohort Study: Departments of Infectious Diseases at Copenhagen University Hospitals, Rigshospitalet (J Gerstoft, N Obel) and Hvidovre (G Kronborg), Odense University Hospital (C Pedersen), Aarhus University Hospitals, Skejby (CS Larsen) and Aalborg (G Pedersen), Herning Hospital (R Mohey), Hillerød Hospital (L Nielsen), and Kolding Hospital (J Jensen).

Disclosures

NO has received research funding from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline, Abbott, Boehringer Ingelheim, Janssen-Cilag, and Swedish Orphan. MGA has received research funding from the research board of Copenhagen University Hospital, Rigshospitalet, and from the Bjørn Astrups fund, and has received travel grants from GSK and Janssen.

The sponsors had no role in the design, conduct, or analysis of the study nor in the decision to publish the manuscript. The authors report no other conflicts of interest in this work.