Operational Research for Cryptococcal Antigen Screening

University of Minnesota3,049 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

SINGLE

Enrollment

3,049

Conditions

Cryptococcal Meningitis Cryptococcus Neoformans Cryptococcosis

Interventions

Eligibility

Sex: ALLMin age: 14 Years

Medical Language ↔ Plain English

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

Locations (2)

Infectious Disease Institute, Makerere University

Kampala, Uganda

Kampala Capital Council Authority Clinics

Kampala, Uganda

Outcomes

Primary Outcomes

Retention in care

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.

Time frame: 6-month

Secondary Outcomes

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

Time frame: 6-month

Survival Time

Survival time among CRAG+ vs. CRAG negative persons with CD4\<100 cells/mcL.

Time frame: 6-month

Uptake of CRAG screening and preemptive treatment

Time frame: baseline

Time from CRAG+ test to receipt of fluconazole therapy

Time frame: 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)

Time frame: 6-month

Percentage of participants with symptomatic cryptococcal meningitis

Time frame: baseline

Risk factors for symptomatic cryptococcal meningitis

Time frame: baseline