A secure analytics platform to study the prognosis of people with HIV in the USA, Canada and Europe and comparative effectiveness of treatment regimens: the Antiretroviral Therapy Cohort Collaboration - The HIV epidemic has changed dramatically since the introduction of effective antiretroviral therapy (ART). As ART regimens and health care for people with HIV (PWH) continue to improve, the population of PWH in North America and Europe is aging. As the treatment landscape changes, it is important to provide up-to-date data on prognosis for PWH in the modern ART era and compare effectiveness of modern ART regimens. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is the largest collaboration of HIV cohorts across North America and Europe, with 20 HIV cohorts and data on around 250,000 PWH on ART. ART-CC pioneered standardized coding of causes of death in treated PWH and has classified causes of death for 16,832 PWH. ART-CC has fostered a collaborative approach to research and enabled researchers across the globe to utilize its data and methodological expertise. Approaches to analyzing data from HIV cohort collaborations have evolved with increasing awareness of the need to protect participants’ privacy, and use of data use agreements to govern data transfers. We will develop a new secure data platform enabling ART-CC collaborators and external researchers to conduct secure, privacy-protecting analyses of pseudonymized ARTCC data using reproducible, shared code. Data will be accessed in a controlled environment, with export of analysis results requiring approval from trained output checkers. This platform will facilitate a distributed model in which researchers from any contributing cohort, and verified external researchers, can conduct analyses, whilst cohorts retain ownership of their data. Research within the platform will incorporate 3 aims. 1) Enhance understanding of cause-specific mortality and cause-specific hospitalizations among PWH, building on ART-CC’s world-leading data on causes of death among PWH and extending these methods to causes of hospitalization. 2) Enhance understanding of prognosis for all-cause mortality in subgroups of PWH. 3) Estimate the comparative effectiveness of novel ART regimens versus older, more commonly used regimens and of GLP-1 agonists, which are increasingly used to address ART-associated weight gain in PWH. ART-CC’s large size and geographical heterogeneity will allow comparisons between US and non-US cohorts. In summary, this proposal will develop a data platform to simplify data sharing for HIV cohorts in North America and Europe, enabling efficient analyses based on open science principles addressing high priority questions in the modern ART era.