Biomarkers of mortality in adults and adolescents with advanced HIV in sub-Saharan Africa.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 Jun 2024
28 Jun 2024
Historique:
received:
15
05
2023
accepted:
30
05
2024
medline:
30
6
2024
pubmed:
30
6
2024
entrez:
29
6
2024
Statut:
epublish
Résumé
One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.
Identifiants
pubmed: 38944653
doi: 10.1038/s41467-024-49317-7
pii: 10.1038/s41467-024-49317-7
doi:
Substances chimiques
Biomarkers
0
Trimethoprim, Sulfamethoxazole Drug Combination
8064-90-2
Anti-HIV Agents
0
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
5492Subventions
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/P022251/1
Organisme : Wellcome Trust (Wellcome)
ID : 108065/Z/15/Z
Informations de copyright
© 2024. The Author(s).
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