Trial reportJournal of acquired immune deficiency syndromes (1999)2019
Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/µL: A Stepped-Wedge, Cluster-Randomized Trial.
Trial report in Journal of acquired immune deficiency syndromes (1999), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01535469 (Operational Research for Cryptococcal Antigen Screening to Improve ART Survival), which is not on this map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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.
Operational Research for Cryptococcal Antigen Screening to Improve ART Survival
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management.Medical mycology · 2020Pooled it
- Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With HIV-Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen Titers.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Trial
- Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial.Medical mycology · 2020Trial
- Headache as a Predictor of Cryptococcal Meningitis in Ambulatory Patients With Symptomatic HIV-associated Cryptococcal Antigenemia.Open forum infectious diseases · 2026Article
- Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review.Frontiers in epidemiology · 2026Review
- Article
- Development of a multiplex-PCR assay for differentiation of Cryptococcus species using the PRP8 gene region.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025Article
- Can liposomal amphotericin B be used as a preventive measure for cryptococcal meningitis?Expert review of anti-infective therapy · 2025Article
- Effectiveness of a National Reflex Laboratory Cryptococcal Antigen Screening Program for People With Advanced HIV Disease in South Africa: A Nationwide-Sampled Cohort Study (CAST-NET).Journal of acquired immune deficiency syndromes (1999) · 2025Article
- Factors associated with cryptococcal capsular antigen positivity among people living with HIV: a retrospective observational cohort study.BMC infectious diseases · 2025Observational
- 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
- Baseline C-reactive Protein as a Risk Factor for Cryptococcal Meningitis and Death in HIV-associated Cryptococcal Antigenemia With CrAg Titer as an Effect Modifier.Open forum infectious diseases · 2024Article
- Impact of Cerebrospinal Fluid Leukocyte Infiltration and Neuroimmmune Mediators on Survival with HIV-Associated Cryptococcal Meningitis.medRxiv : the preprint server for health sciences · 2024Article
- Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda.PloS one · 2024Article
- Diagnosis and management of cryptococcal meningitis in HIV-infected adults.Clinical microbiology reviews · 2023Review
- Cryptococcal meningitis.Nature reviews. Disease primers · 2023Review
- Advanced HIV disease: A review of diagnostic and prophylactic strategies.HIV medicine · 2023Review
- Preemptive Therapy in Cryptococcosis Adjusted for Outcomes.Journal of fungi (Basel, Switzerland) · 2023Article
- Outpatient Cryptococcal Antigen Screening Is Associated With Favorable Baseline Characteristics and Improved Survival in Persons With Cryptococcal Meningitis in Uganda.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Six months survival and risk factors for attrition for patients detected with cryptococcal antigenemia through screening in Malawi.PloS one · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS.
methodsWe enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps.
resultsWe included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160.
conclusionsWe observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.
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Registered trials
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