The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) has represented Region 1 of the leDEA initiative since 2006. The 23 single and multi-site clinical and classical epidemiologic HIV cohorts of the NA-ACCORD encompass most HIV cohorts within the US and Canada. Over 100 sites contribute data collected from over 190,000 people with HIV (PWH). We have established a strong collaborative infrastructure that capitalizes on the talents and expertise of a multi-disciplinary group of investigators that span basic science, clinical research, epidemiology, data informatics and biostatistics. We have been highly productive in addressing our previous Aims and key questions in contemporary care and public health relevant to adult PWH. Our strengths are especially relevant to the goals of the US DHHS Ending the HIV Epidemic (EHE) initiative, uniquely providing the broad geographic and demographic scope, established scientific platform, large sample size, extensive longitudinal follow-up of >1.3 million person-years, and depth of clinical data to inform the goals of EHE with rich data on those who will continue to survive with HIV after transmission is halted. With the onset of the COVID-19 pandemic, questions regarding the impact of COVID-19 on HIV outcomes and trends in HIV indicators, as well as longer-term outcomes of COVID-19 among PWH, can be answered in the NA-ACCORD. Within this context, we present three broadly-defined aims for the next funding cycle: Aim 1: Characterize the longitudinal course of HIV treatment, progression and outcomes in North America in the setting of the EHE initiative, which will increase the number and heterogeneity of those in HIV care as HIV treatment and the long-term challenges of living with HIV continue to evolve. Aim 2: To assess and characterize the clinical course of HIV infection in North America, with a focus on major non-AIDS comorbidities and co-infections, multimorbidity and comorbidity- free life expectancy. Aim 3: To expand and extend our state-of-the art epidemiologic, biostatistical, and data science methodologic approaches. The NA-ACCORD is a world-class collaboration of established HIV cohorts well-positioned to a) provide in-depth understanding of the longitudinal course of HIV when extraordinary efforts are being made to EHE; b) collaborate with the other IeDEA regions to inform the future HIV epidemics in low- and middle-income regions; and c) understand differences in HIV treatment, outcomes and prognostic factors that will inform future research and HIV care globally.