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.
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
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
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Treatment groupsSee each treatment group below.