Epstein–Barr virus and cytomegalovirus co-infections and mortality risk in patients with HIV-associated cryptococcal meningitis: a post-hoc analysis of a prospective nested cohort in the AMBITION-cm randomised controlled trial
Notice bibliographique
Résumé
BACKGROUND: HIV-associated cryptococcal meningitis case fatality remains greater than 25%. Co-prevalent infections might contribute to poor outcomes. We aimed to ascertain the prevalence and the clinical significance of Epstein-Barr virus (EBV) and cytomegalovirus co-infections in patients with cryptococcal meningitis to guide potential therapeutic interventions. METHODS: We conducted a post-hoc analysis of a prospective cohort using plasma and cerebrospinal fluid (CSF) samples collected in the AMBITION-cm randomised trial. AMBITION-cm was done at seven hospital sites across five African countries (Botswana, Malawi, South Africa, Uganda, and Zimbabwe). The primary endpoint of the trial was all-cause mortality at 10 weeks. Quantitative PCR (qPCR) was used to measure baseline cytomegalovirus and EBV viral loads in these samples. Baseline demographic and clinical data including antiretroviral therapy status, and laboratory data including CD4 cell count, CSF white cell count, protein, glucose, and quantitative cryptococcal culture were captured in real time via an electronic medical records system. We assessed the prevalence of cytomegalovirus plasma viraemia and EBV plasma viraemia, and CNS co-infections, associations between cytomegalovirus and EBV co-infection status and baseline covariates, and associations with 2-week and 10-week mortality. FINDINGS: Between Jan 31, 2018, and Feb 18, 2021, among 811 participants enrolled, 60% were male, median age was 37 years (IQR 32-43), and median baseline CD4 count was 27 cells per μL (IQR 10-58). Cytomegalovirus plasma viraemia was present in 395 (49%) of 804 participants and EBV plasma viraemia was present in 585 (73%) participants. 39 (5%) of 707 participants had detectable cytomegalovirus in the CSF and 191 (27%) of 708 participants had detectable EBV. Cytomegalovirus plasma viraemia was associated with lower CD4 cell counts, less CSF inflammation, and higher CSF fungal burdens. Conversely, EBV plasma viraemia was associated with higher CD4 cell counts and more CSF inflammation. At 2 and 10 weeks, the risk of mortality was two times higher in participants with high-level cytomegalovirus plasma viraemia (≥1000 copies per mL) than in participants without cytomegalovirus plasma viraemia (adjusted odds ratio 2·31 [95% CI 1·12-4·75] at 2 weeks; 2·44 [1·33-4·45] at 10 weeks). EBV coinfections were not associated with increased mortality. INTERPRETATION: These data indicate that cytomegalovirus might be an important copathogen in this context, and that cytomegalovirus viraemia represents a potentially modifiable risk factor to reduce mortality among adults with HIV-associated cryptococcal meningitis. Interventional trials are now required and planned to determine whether treatment of cytomegalovirus viraemia improves outcomes in advanced HIV disease. FUNDING: National Institute for Health and Care Research, European and Developing Countries Clinical Trials Partnership, Medical Research Council, and Wellcome Trust.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».