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Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Afr...

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Autores principales: Kitonsa, Jonathan, Nsubuga, Rebecca, Mayanja, Yunia, Kiwanuka, Julius, Nikweri, Yofesi, Onyango, Martin, Anywaine, Zacchaeus, Ggayi, Abu-Baker, Kibengo, Freddie Mukasa, Kaleebu, Pontiano, Day, Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728283/
https://www.ncbi.nlm.nih.gov/pubmed/33253210
http://dx.doi.org/10.1371/journal.pntd.0008823
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author Kitonsa, Jonathan
Nsubuga, Rebecca
Mayanja, Yunia
Kiwanuka, Julius
Nikweri, Yofesi
Onyango, Martin
Anywaine, Zacchaeus
Ggayi, Abu-Baker
Kibengo, Freddie Mukasa
Kaleebu, Pontiano
Day, Jeremy
author_facet Kitonsa, Jonathan
Nsubuga, Rebecca
Mayanja, Yunia
Kiwanuka, Julius
Nikweri, Yofesi
Onyango, Martin
Anywaine, Zacchaeus
Ggayi, Abu-Baker
Kibengo, Freddie Mukasa
Kaleebu, Pontiano
Day, Jeremy
author_sort Kitonsa, Jonathan
collection PubMed
description Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02–2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94–0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32–4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.
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spelling pubmed-77282832020-12-17 Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda Kitonsa, Jonathan Nsubuga, Rebecca Mayanja, Yunia Kiwanuka, Julius Nikweri, Yofesi Onyango, Martin Anywaine, Zacchaeus Ggayi, Abu-Baker Kibengo, Freddie Mukasa Kaleebu, Pontiano Day, Jeremy PLoS Negl Trop Dis Research Article Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02–2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94–0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32–4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions. Public Library of Science 2020-11-30 /pmc/articles/PMC7728283/ /pubmed/33253210 http://dx.doi.org/10.1371/journal.pntd.0008823 Text en © 2020 Kitonsa et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kitonsa, Jonathan
Nsubuga, Rebecca
Mayanja, Yunia
Kiwanuka, Julius
Nikweri, Yofesi
Onyango, Martin
Anywaine, Zacchaeus
Ggayi, Abu-Baker
Kibengo, Freddie Mukasa
Kaleebu, Pontiano
Day, Jeremy
Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
title Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
title_full Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
title_fullStr Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
title_full_unstemmed Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
title_short Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda
title_sort determinants of two-year mortality among hiv positive patients with cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in uganda
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728283/
https://www.ncbi.nlm.nih.gov/pubmed/33253210
http://dx.doi.org/10.1371/journal.pntd.0008823
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