The three countries within the East African leDEA Regional Consortium (Kenya, Uganda, Tanzania) have adult HIV prevalence rates ranging between 5-10%.Since the advent of the global antiretroviral therapy (ART) rollout in 2003, there has been a dramatic increase in the percent coverage of those estimated in need of ART (based on the 2006 WHO guidelines), from essentially no patients on in 2003, to 65% coverage in Kenya, 53% in Uganda, and 44% in Tanzania by the end of 2009. Though this dramatic scale-up of HIV treatment has had a positive impact on mortality rates, key questions remain throughout the course of a patient's engagement in care, from the pre- ART period through ART-initiation, initial clinical response to ART and regimen durability (occurrence of adverse events and drug resistance), to long-term maintenance, loss to follow-up (LTFU), and death. It is the long-range goal of this consortium is to provide answers to the questions that clinicians, programs, and ministries of health consider fundamental to the evolution and sustainability of their long term HIV care and treatment strategies. In the next funding cycle, we will address these questions by enhancing data collection in key areas as well as merging existing data sources to better assess and inform the ART rollout in East Africa. We are optimally placed to lead this endeavor as our consortium includes representative HIV-clinics, a harmonized regional database, as well as physicians, epidemiologists, and analysts with expertise in implementation research and a solid understanding of the strengths and limitations of existing data sources. Our top priorities for the next phase of the EA-leDEA Consortium are to: Aim 1: Determine the short and long-term outcomes of adults and children along the entire spectrum of HIV care and examine patient and site-level factors associated with these outcomes; Aim 2: Assess the penetrance and outcomes of prevention of mother to child transmission of HIV (pMTCT) strategies; Aim 3: Monitor the translation of evidence into practice for managing co-infections with an emphasis on Tuberculosis (TB); Aim 4: Determine the prevalence, incidence, determinants and outcomes of malignancies in East Africa with a focus on Kaposi's sarcoma (KS) and cervical cancer. RELEVANCE: Through these efforts, we will enhance our understanding about the HIV-epidemic in its sub- Saharan Africa context, provide insights on the optimal structure and impact of care and treatment programs, expand the set of tools available to inform implementation and operations research in resource-constrained settings and inform policy among stakeholders and decision makers at every level in the region as well as the broader HIV/AIDS scientific community.