Abstract Early mortality among patients initiating ART is a significant challenge to the success of HIV treatment programs. A leading contributor to this early mortality is cryptococcal meningitis, a fungal disease that is among the leading opportunistic infections among HIV-infected persons in Southeast Asia. Mortality from cryptococcal meningitis ranges from 30-70%, even with optimal care. Cryptococcal antigenemia (CrAg) - a diagnostic finding for infection which is highly predictive for future development of meningitis and which serves as an independent predictor of death in HIV-infected patients - can be detected three weeks to three months before meningitis occurs. Screening for CrAg at ART initiation in high-risk patients (those with CD4+ T-cell counts of <100 cells/l) can allow for earlier treatment of infection, which can improve patient retention-in-care as it prevents early mortality. Although the WHO has recommended screening for CrAg among high-risk patients in settings with a high prevalence of cryptococcal disease, the effectiveness of such screening programs on patient retention in care in Vietnam has not been investigated. We propose a project that utilizes a stepped-wedge design to evaluate changes in patient retention-in-care and survival following the implementation of a CrAg screening program in Vietnam. The main objectives will be to define baseline prevalence of cryptococcal infection in geographic areas and to investigate the cost-effectiveness of this screening program in Vietnam. The will also allow us to improve laboratory capacity to diagnose cryptococcosis using an antigen-based assay, and conduct implementation science to evaluate best practices in rolling out such a program. If successful in improving patient retention-in-care and reducing cryptococcal meningitis-associated mortality, screening and subsequent treatment could shift current clinical paradigms for the benefit of HIV-infected patients in Vietnam.