Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes

Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes.Methods. Five hundred one patients with HIV-associated CM were followed prospecti...

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Main Authors: Joseph N. Jarvis, Tihana Bicanic, Angela Loyse, Daniel Namarika, Arthur Jackson, Jesse C. Nussbaum, Nicky Longley, Conrad Muzoora, Jacob Phulusa, Kabanda Taseera, Creto Kanyembe, Douglas Wilson, Mina C. Hosseinipour, Annemarie E. Brouwer, Direk Limmathurotsakul, Nicholas White, Charles Van Der Horst, Robin Wood, Graeme Meintjes, John Bradley, Shabbar Jaffar, Thomas Harrison
Other Authors: St George's University of London
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Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/34286
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spelling th-mahidol.342862018-11-09T09:39:48Z Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes Joseph N. Jarvis Tihana Bicanic Angela Loyse Daniel Namarika Arthur Jackson Jesse C. Nussbaum Nicky Longley Conrad Muzoora Jacob Phulusa Kabanda Taseera Creto Kanyembe Douglas Wilson Mina C. Hosseinipour Annemarie E. Brouwer Direk Limmathurotsakul Nicholas White Charles Van Der Horst Robin Wood Graeme Meintjes John Bradley Shabbar Jaffar Thomas Harrison St George's University of London University of Cape Town London School of Hygiene &amp; Tropical Medicine University of North Carolina Project University of California, San Francisco Mbarara University of Science and Technology Edendale Hospital Radboud University Nijmegen Medical Centre Mahidol University Nuffield Department of Clinical Medicine Imperial College London Medicine Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes.Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality.Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 × 109cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age.In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P =. 007), but not with time to initiation of antiretroviral therapy (ART).Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes. © 2013 The Author. 2018-11-09T02:39:48Z 2018-11-09T02:39:48Z 2014-03-01 Article Clinical Infectious Diseases. Vol.58, No.5 (2014), 736-745 10.1093/cid/cit794 15376591 10584838 2-s2.0-84894235223 https://repository.li.mahidol.ac.th/handle/123456789/34286 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84894235223&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Medicine
spellingShingle Medicine
Joseph N. Jarvis
Tihana Bicanic
Angela Loyse
Daniel Namarika
Arthur Jackson
Jesse C. Nussbaum
Nicky Longley
Conrad Muzoora
Jacob Phulusa
Kabanda Taseera
Creto Kanyembe
Douglas Wilson
Mina C. Hosseinipour
Annemarie E. Brouwer
Direk Limmathurotsakul
Nicholas White
Charles Van Der Horst
Robin Wood
Graeme Meintjes
John Bradley
Shabbar Jaffar
Thomas Harrison
Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes
description Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes.Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality.Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10colony-forming units/mL increase; 95% CI, 1.0-1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4-11.1), high peripheral white blood cell count (>10 × 109cells/L; OR, 8.7; 95% CI, 2.5-30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age.In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P =. 007), but not with time to initiation of antiretroviral therapy (ART).Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes. © 2013 The Author.
author2 St George's University of London
author_facet St George's University of London
Joseph N. Jarvis
Tihana Bicanic
Angela Loyse
Daniel Namarika
Arthur Jackson
Jesse C. Nussbaum
Nicky Longley
Conrad Muzoora
Jacob Phulusa
Kabanda Taseera
Creto Kanyembe
Douglas Wilson
Mina C. Hosseinipour
Annemarie E. Brouwer
Direk Limmathurotsakul
Nicholas White
Charles Van Der Horst
Robin Wood
Graeme Meintjes
John Bradley
Shabbar Jaffar
Thomas Harrison
format Article
author Joseph N. Jarvis
Tihana Bicanic
Angela Loyse
Daniel Namarika
Arthur Jackson
Jesse C. Nussbaum
Nicky Longley
Conrad Muzoora
Jacob Phulusa
Kabanda Taseera
Creto Kanyembe
Douglas Wilson
Mina C. Hosseinipour
Annemarie E. Brouwer
Direk Limmathurotsakul
Nicholas White
Charles Van Der Horst
Robin Wood
Graeme Meintjes
John Bradley
Shabbar Jaffar
Thomas Harrison
author_sort Joseph N. Jarvis
title Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes
title_short Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes
title_full Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes
title_fullStr Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes
title_full_unstemmed Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: Implications for improving outcomes
title_sort determinants of mortality in a combined cohort of 501 patients with hiv-associated cryptococcal meningitis: implications for improving outcomes
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/34286
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