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Cryptococcal meningitis is a major cause of death among people with human immunodeficiency virus (PWH). Cryptococcal antigen (CrAg) testing of asymptomatic patients is an important public health measure to reduce mortality in high-incidence areas. However, limited data exist on CrAg prevalence in Central America. We conducted a prospective cohort study at the 2 largest human immunodeficiency virus (HIV) clinics and hospitals in Honduras. Cryptococcal antigen in serum and cerebrospinal fluid was performed in individuals with HIV who had CD