Cryptococcal Meningitis, Cryptococcosis, Cryptococcus Neoformans
Conditions
Keywords
cryptococcal meningitis, hiv, aids, implementation science, stepped wedge design, retention-in-care
Brief summary
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
Interventions
DRUGFluconazole
Fluconazole 800mg orally daily for 2 weeks, then 400mg daily for 8 weeks
Sponsors
Infectious Diseases Institute, Uganda
Makerere University
Centers for Disease Control and Prevention
University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention in care | 6-month | 1. before/after CRAG screening implementation (All persons) 2. CRAG positive persons treated with high-dose fluconazole as compared to 6-month survival of CRAG negative persons who are eligible for antiretroviral therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cryptococcal meningitis-free survival time | 6-month | 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 |
| Survival Time | 6-month | Survival time among CRAG+ vs. CRAG negative persons with CD4\<100 cells/mcL. |
| 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 | 6-month | Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event) |
| Percentage of participants with symptomatic cryptococcal meningitis | baseline | — |
| Risk factors for symptomatic cryptococcal meningitis | baseline | — |
Countries
Uganda
Outcome results
None listed