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

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.