ArticleJournal of acquired immune deficiency syndromes (1999)2017
The CSF Immune Response in HIV-1-Associated Cryptococcal Meningitis: Macrophage Activation, Correlates of Disease Severity, and Effect of Antiretroviral Therapy.
Article in Journal of acquired immune deficiency syndromes (1999), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Cytoplasmic NAD/H synthesis via NRK1 regulates inflammatory capacity and promotes survival of CD4Nature communications · 2026Article
- Cerebrospinal Fluid Mononuclear Cell Phenotype and Activation Predictors of 2-Week and 1-Year Survival Among Persons With HIV-Associated Cryptococcal Meningitis.The Journal of infectious diseases · 2025Article
- Brain-infiltrating CD4 T cells drive inflammatory microglia proliferation during cryptococcal meningitis in mice.Nature communications · 2025Article
- Recent Antiretroviral Therapy Initiation Is Associated With Increased Mortality Risk in HIV-associated Cryptococcal Meningitis: An Analysis of Clinical Trial Data From Africa.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- The hypervirulent Type-1/Type-17 phenotype ofInfection and immunity · 2025Article
- Relative Contribution of Pharmacokinetics and Immune Signatures to Clinical Outcomes in Patients With HIV-associated Cryptococcal Meningitis.Open forum infectious diseases · 2025Article
- Cerebrospinal Fluid Cytokines and Chemokines Involved in Cytotoxic Cell Function and Risk of Acute 14-Day Mortality in Persons with Advanced HIV and Cryptococcal Meningitis.The Journal of infectious diseases · 2025Article
- Cytokine dynamics in the blood and cerebrospinal fluid of HIV/AIDS patients with cryptococcal meningitis receiving antifungal therapy.Frontiers in cellular and infection microbiology · 2025Article
- Clinical importance of cerebrospinal fluid protein levels in HIV-associated cryptococcal meningitis: Insights from a prospective cohort study in Uganda.Medical mycology · 2024Article
- Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy.BMC neurology · 2024Article
- Molecular Diagnostics ofDiseases (Basel, Switzerland) · 2024Review
- Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis.medRxiv : the preprint server for health sciences · 2023Article
- Cryptococcal meningitis.Nature reviews. Disease primers · 2023Review
- Immune responses to human fungal pathogens and therapeutic prospects.Nature reviews. Immunology · 2023Review
- The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways.International journal of molecular sciences · 2023Review
- Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments.Microorganisms · 2022Review
- Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients.Clinical and experimental immunology · 2021Article
- A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis.BMC infectious diseases · 2021Article
- Clinical characteristics,The Journal of international medical research · 2021Article
- Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches.Life (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
10 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundImmune modulation may improve outcome in HIV-associated cryptococcal meningitis. Animal studies suggest alternatively activated macrophages are detrimental but human studies are limited. We performed a detailed assessment of the cerebrospinal fluid (CSF) immune response and examined immune correlates of disease severity and poor outcome, and the effects of antiretroviral therapy (ART). METHODOLOGY: We enrolled persons ≥18 years with first episode of HIV-associated cryptococcal meningitis. CSF immune response was assessed using flow cytometry and multiplex cytokine analysis. Principal component analysis was used to examine relationships between immune response, fungal burden, intracranial pressure and mortality, and the effects of recent ART initiation (<12 weeks).
findingsCSF was available from 57 persons (median CD4 34/μL). CD206 (alternatively activated macrophage marker) was expressed on 54% CD14 and 35% CD14 monocyte-macrophages. High fungal burden was not associated with CD206 expression but with a paucity of CD4, CD8, and CD4CD8 T cells and lower interleukin-6, G-CSF, and interleukin-5 concentrations. High intracranial pressure (≥30 cm H2O) was associated with fewer T cells, a higher fungal burden, and larger Cryptococcus organisms. Mortality was associated with reduced interferon-gamma concentrations and CD4CD8 T cells but lost statistical significance when adjusted for multiple comparisons. Recent ART was associated with increased CSF CD4/CD8 ratio and a significantly increased macrophage expression of CD206.
conclusionsPaucity of CSF T cell infiltrate rather than alternative macrophage activation was associated with severe disease in HIV-associated cryptococcosis. ART had a pronounced effect on the immune response at the site of disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.