Optimizing Care for Cryptococcal Antigenemia: Evaluation of Short Course Fluconazole and ART Timing Among CrAg+ Persons With Low Titers

Sponsor
University of Minnesota
Study ID
NCT07743593
Phase
PHASE3
Status
Not Yet Recruiting

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Conditions

  • Cryptococcal Antigenemia
  • Cryptococcal Infection
  • Cryptococcal Meningitis
  • HIV-1-infection

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Immediate ART Initiation — DRUG
    Antiretroviral therapy will be initiated immediately at enrollment for participants randomized to immediate ART initiation. ART drug choice will be per clinical standard of care.
  • Delayed ART Initiation — DRUG
    Antiretroviral therapy will be initiated 14 days after enrollment for participants randomized to delayed ART initiation. ART drug choice will be per clinical standard of care.
  • 10-Week Fluconazole — DRUG
    Participants will receive fluconazole 800 mg daily for 14 days, followed by fluconazole 400 mg daily through week 10, then stop fluconazole.
  • 24-Week Fluconazole — DRUG
    Participants will receive fluconazole 800 mg daily for 14 days, followed by fluconazole 400 mg daily through week 10, then fluconazole 200 mg daily for an additional 14 weeks, for a total fluconazole duration of 24 weeks.

Study Details

This randomized clinical trial will evaluate the optimal duration of fluconazole therapy and timing of antiretroviral therapy initiation among HIV-infected persons with asymptomatic cryptococcal antigenemia and low cryptococcal antigen titers in Uganda. Participants with low-titer cryptococcal antigenemia will be followed to assess whether a shorter 10-week course of fluconazole is non-inferior to the standard 24-week fluconazole regimen for 24-week cryptococcal meningitis-free survival. Among participants eligible for antiretroviral therapy timing randomization, the study will also compare immediate antiretroviral therapy initiation with delayed initiation after 14 days to evaluate 10-week hospitalization-free survival. Participants will be followed for up to 24 weeks, with study visits and contacts to assess survival, cryptococcal meningitis, hospitalizations, adverse events, and fluconazole adherence.

Key Dates

First listed
Aug 4, 2026
Start date
Jan 5, 2027
Status verified
Sep 2026
Primary completion
Aug 30, 2031
Completion
Aug 30, 2031

Study Design

Enrollment
505 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Immediate ART + 10-Week Fluconazole Arm Type:
    Participants eligible for ART timing randomization will initiate antiretroviral therapy immediately at enrollment. Participants who are alive and have not developed cryptococcal meningitis at week 10 will stop fluconazole after completing 10 weeks of preemptive fluconazole therapy.
  • Experimental: Immediate ART + 24-Week Fluconazole
    Participants eligible for ART timing randomization will initiate antiretroviral therapy immediately at enrollment. Participants who are alive and have not developed cryptococcal meningitis at week 10 will continue fluconazole through 24 weeks of preemptive fluconazole therapy.
  • Experimental: Delayed ART + 10-Week Fluconazole
    Participants eligible for ART timing randomization will delay antiretroviral therapy initiation until 14 days after enrollment. Participants who are alive and have not developed cryptococcal meningitis at week 10 will stop fluconazole after completing 10 weeks of preemptive fluconazole therapy.
  • Active Comparator: Delayed ART + 24-Week Fluconazole
    Participants eligible for ART timing randomization will delay antiretroviral therapy initiation until 14 days after enrollment. Participants who are alive and have not developed cryptococcal meningitis at week 10 will continue fluconazole through 24 weeks of preemptive fluconazole therapy.
  • Experimental: ART-Experienced + 10-Week Fluconazole
    Participants who are already receiving ART or are not eligible for ART timing randomization will continue ART per standard clinical care. Participants who are alive and have not developed cryptococcal meningitis at week 10 will stop fluconazole after completing 10 weeks of preemptive fluconazole therapy.
  • Active Comparator: ART-Experienced + 24-Week Fluconazole
    Participants who are already receiving ART or are not eligible for ART timing randomization will continue ART per standard clinical care. Participants who are alive and have not developed cryptococcal meningitis at week 10 will continue fluconazole through 24 weeks of preemptive fluconazole therapy.

Primary Outcome Measure

24-week cryptococcal meningitis-free survival with retention in care [ Time Frame: 24 weeks ]

Central Contacts

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