A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Abstract Cryptococcus remains the leading cause of HIV-related meningitis. Cryptococcal antigenemia (CrAg) is detectable weeks before onset of meningitis, offering a critical window for intervention. Conflicting guidelines on the timing of antiretroviral therapy (ART) initiation among asymptomatic CrAg+ persons result in potentially harmful delays for those with advanced HIV disease. Additionally, 10 weeks of preemptive fluconazole therapy for CrAg+ persons has demonstrated a 28% survival benefit in trials, yet current WHO guidelines—based on expert opinion alone—recommend an extended 6-month fluconazole treatment course. These inefficiencies drive unnecessary costs, excessive antifungal exposure, and missed opportunities for streamlined care. Objective: To inform international guidelines by rigorously evaluating: 1. The safest and most effective timing for ART initiation to maximize survival; 2. The optimal duration of fluconazole therapy for asymptomatic CrAg+ persons with low titers (<1:80). Methods: We propose a highly innovative sequential randomized clinical trial (RCT) in Uganda involving 505 CrAg+ persons with low plasma titers (<1:80): Aim 1: Determine whether immediate ART initiation yields non-inferior 10-week hospitalization-free survival compared to the current standard-of-care 2-week delay. Hypothesis: If immediate ART is safe and effective, this could eliminate unnecessary delays in lifesaving HIV care and streamline HIV care pathways globally. Aim 2: Determine whether a short 10-week course of fluconazole achieves non-inferior 24-week meningitis- free survival compared to the WHO-recommended 24-week regimen. Hypothesis: If 10 weeks of fluconazole preemptive therapy is non-inferior, this will reduce unnecessary antifungal exposure, drug toxicity, and costs. Innovation: This trial challenges the outdated one-size-fits-all approach by introducing treatment stratification based on CrAg titer levels, a biomarker for cryptococcal burden. Our results will directly address current gaps in treatment for CrAg+ persons, aligning guidelines with evidence-based care to improve survival, potentially reduce unnecessary antifungal exposure, and optimize resource use. Impact: This trial has the potential to redefine global HIV and cryptococcal care by: 1. Resolving uncertainty around ART timing to prevent harmful delays and reduce mortality, 2. Establishing the optimal duration of fluconazole therapy for people with low CrAg titers, 3. Informing and harmonizing WHO, U.S., and national treatment guidelines for cryptococcal prevention. We will generate evidence to maximize survival, streamline ART initiation, and optimize antifungal treatment for people with advanced HIV disease globally. This evidence-based approach will empower policymakers to optimize care for millions of people with advanced HIV disease and reduce AIDS-related deaths.
Grant Summary
A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $446K for university, nonprofit, healthcare org. Applications are due 2031-07-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $446K
2031-07-31
- 1Confirm your organization is eligible for A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection: Frequently Asked Questions
Who is eligible for the A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection?
A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection provide?
A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection provides up to $446K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection deadline?
Applications for A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection are due 2031-07-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection?
To apply for A randomized trial to evaluate the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.