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.
Inclusion Criteria:
Exclusion Criteria:
radha@umn.edu
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.
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.
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.
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.
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.
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.
Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis
Early Versus Delayed Antiretroviral Therapy (ART) in the Treatment of Cryptococcal Meningitis in Africa
Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Sub-saharan Africa
High-Dose Fluconazole for the Treatment of Cryptococcal Meningitis in HIV-Infected Individuals