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.

Inclusion Criteria: * HIV-1 infection * Age greater than 18 years * Ability and willingness to give informed consent * Plasma or serum cryptococcal antigen positive with titer less than 1:160 Exclusion Criteria: * Cannot or unlikely to attend regular clinic visits * History of cryptococcal infection * Symptomatic meningitis confirmed by cerebrospinal fluid cryptococcal antigen positivity * More than 10 weeks of fluconazole therapy * Pregnancy confirmed by urinary or serum pregnancy test * Current breastfeeding