Operational Research for Cryptococcal Antigen Screening

Study Overview
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Brief Summary
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This will be a stepped wedge randomized trial design to evaluate the implementation of cryptococcal antigen (CRAG) screening and preemptive anti-fungal therapy of HIV-infected persons entering antiretroviral therapy (ART) outpatient treatment in Uganda. Those who are ART eligible with a CD4≤100 cells/mcL will have a serum/plasma CRAG performed by lateral flow assay. Those who are CRAG-positive and asymptomatic will be treated with high dose fluconazole. After 6 months survival with retention-in-care will be compared between those who are CRAG+ and CRAG negative

Official Title
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Operational Research for Cryptococcal Antigen Screening to Improve ART Survival

Conditions
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Cryptococcal Meningitis, Cryptococcus Neoformans, Cryptococcosis

Intervention / Treatment
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* Drug: Fluconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection CD4≤100 cells/mcL Cryptococcal antigen (CRAG) positive age >14 years Exclusion Criteria: Suspected Cryptococcal meningitis Prior known history of cryptococcal meningitis currently receiving HIV antiretroviral therapy Allergy to any azole antifungal medication Persons with known serious hepatic co-morbidities, transaminitis, or clinical jaundice who should not receive fluconazole in the opinion of the study investigator. Current known pregnancy

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CrAg Screening and Fluconazole<br>Cryptococcal Antigen (CrAg) Screening with preemptive antifungal treatment per World Health Organization (WHO) guidelines. Randomized Stepped Wedge design of phased implementation. | Drug: Fluconazole<br>* Fluconazole 800mg orally daily for 2 weeks, then 400mg daily for 8 weeks<br>* Other names: Diflucan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention in care | before/after CRAG screening implementation (All persons) CRAG positive persons treated with high-dose fluconazole as compared to 6-month survival of CRAG negative persons who are eligible for antiretroviral therapy. | 6-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cryptococcal meningitis-free survival time | Cryptococcal meningitis-free survival time in those who are asymptomatic CRAG positive and treated with fluconazole compared to CRAG-negative persons with CD4<100 cells/mcL | 6-month | 
| Survival Time | Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL. | 6-month | 
| Uptake of CRAG screening and preemptive treatment |  | baseline | 
| Time from CRAG+ test to receipt of fluconazole therapy |  | Days from CD4 testing | 
| All-cause discontinuation of fluconazole | Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event) | 6-month | 
| Percentage of participants with symptomatic cryptococcal meningitis |  | baseline | 
| Risk factors for symptomatic cryptococcal meningitis |  | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cryptococcal meningitis, hiv, aids, implementation science, stepped wedge design, retention-in-care