Trial reportThe Journal of infectious diseases2015
Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial.
Trial report in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01075152 (Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis), which is not on this map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.Nature communications · 2024Pooled it
- Trial of High-Dose Oral Rifampin in Adults with Tuberculous Meningitis.The New England journal of medicine · 2025Trial
- Differences in Immunologic Factors Among Patients Presenting with Altered Mental Status During Cryptococcal Meningitis.The Journal of infectious diseases · 2017Trial
- HIV-1 compartmentalization in the central nervous system during cryptococcal meningitis: Analysis of viral, fungal, and host factors.PLoS pathogens · 2026Article
- Revisiting Immune-Mediated Mechanisms as Drivers of Cryptococcal Immune Reconstitution Inflammatory Syndrome.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Cryptococcal Meningitis Treatment Beyond HIV: Recognizing the Need for Individualized Immune-Based Strategies.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 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
- Tuberculous meningitis associated with the absence of pleocytosis in cerebrospinal fluid in an immunocompetent patient: A case report.IJID regions · 2024Article
- Clinical importance of cerebrospinal fluid protein levels in HIV-associated cryptococcal meningitis: Insights from a prospective cohort study in Uganda.Medical mycology · 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
- Importance of Clinical Isolates inJournal of fungi (Basel, Switzerland) · 2023Review
- Immunological correlates of protection following vaccination with glucan particles containing Cryptococcus neoformans chitin deacetylases.NPJ vaccines · 2023Article
- Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality.Journal of fungi (Basel, Switzerland) · 2022Article
- Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments.Microorganisms · 2022Review
- Therapeutic Lumbar Punctures in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: Should Opening Pressure Direct Management?Open forum infectious diseases · 2022Article
- Review
- Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
introductionEarlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1-2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome.
methodsThree macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis.
resultsMore participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation.
conclusionsEarly ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated.
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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.