Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.
AIDS-Related Opportunistic Infections
/ drug therapy
Adult
Amphotericin B
/ therapeutic use
Anti-Inflammatory Agents
/ therapeutic use
Antifungal Agents
/ therapeutic use
Body Weight
Cohort Studies
Coma
Dexamethasone
/ therapeutic use
Female
Fluconazole
/ therapeutic use
Humans
Male
Meningitis, Cryptococcal
/ drug therapy
Retrospective Studies
Risk Factors
Seizures
Uganda
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
21
07
2020
accepted:
03
10
2020
revised:
10
12
2020
pubmed:
1
12
2020
medline:
23
1
2021
entrez:
30
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33253210
doi: 10.1371/journal.pntd.0008823
pii: PNTD-D-20-01312
pmc: PMC7728283
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antifungal Agents
0
Dexamethasone
7S5I7G3JQL
Amphotericin B
7XU7A7DROE
Fluconazole
8VZV102JFY
Types de publication
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0008823Subventions
Organisme : Medical Research Council
ID : G1100684
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00027/1
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist
Références
AIDS. 2002 May 3;16(7):1031-8
pubmed: 11953469
N Engl J Med. 1997 Jul 3;337(1):15-21
pubmed: 9203426
N Engl J Med. 2016 Feb 11;374(6):542-54
pubmed: 26863355
Clin Infect Dis. 1999 Feb;28(2):291-6
pubmed: 10064246
PLoS One. 2012;7(12):e51291
pubmed: 23251485
Clin Epidemiol. 2014 May 13;6:169-82
pubmed: 24872723
J Infect. 2012 Jan;64(1):76-81
pubmed: 22079502
Ann Intern Med. 2011 Aug 16;155(4):209-16
pubmed: 21768555
J Fungi (Basel). 2017 Dec 02;3(4):
pubmed: 29371581
Open Forum Infect Dis. 2019 Nov 05;6(11):ofz478
pubmed: 32042847
AIDS. 2009 Feb 20;23(4):525-30
pubmed: 19182676
N Engl J Med. 2014 Jun 26;370(26):2487-98
pubmed: 24963568
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD005647
pubmed: 18843697
Soc Sci Med. 2004 Apr;58(7):1353-66
pubmed: 14759681
Clin Infect Dis. 2012 Jan 1;54(1):121-8
pubmed: 22052885
Clin Infect Dis. 2020 Jan 16;70(3):521-524
pubmed: 31155650
Curr Clin Microbiol Rep. 2016;3:92-102
pubmed: 27257597
Lancet Infect Dis. 2016 Jul;16(7):809-818
pubmed: 26971081
Clin Infect Dis. 2019 Apr 24;68(9):1494-1501
pubmed: 30169607
Clin Infect Dis. 2014 Mar;58(5):736-45
pubmed: 24319084
Lancet Infect Dis. 2014 Apr;14(4):281-90
pubmed: 24602844
Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647
pubmed: 30045416
Trials. 2014 Nov 12;15:441
pubmed: 25391338
Clin Infect Dis. 2008 Jun 1;46(11):1694-701
pubmed: 18433339
AIDS. 2012 Jul 17;26(11):1363-70
pubmed: 22526517
Lancet Infect Dis. 2017 Aug;17(8):873-881
pubmed: 28483415
AIDS. 2011 Jul 17;25(11):1405-14
pubmed: 21572308
J Acquir Immune Defic Syndr. 2007 Aug 15;45(5):555-9
pubmed: 17577124
Qual Life Res. 2005 Jun;14(5):1301-10
pubmed: 16047505
J Infect. 2001 Nov;43(4):226-33
pubmed: 11869059
BMC Infect Dis. 2010 Mar 15;10:67
pubmed: 20230635
BMC Neurol. 2014 Oct 13;14:208
pubmed: 25307800
N Engl J Med. 2013 Apr 4;368(14):1291-1302
pubmed: 23550668