The need for organ transplantation in HIV-positive individuals is growing due to a rising prevalence of end-stage renal and liver disease. Excellent outcomes of transplantation in HIV-positive individuals have been achieved using HIV-negative donors. However, due to a major organ shortage and a high waitlist mortality for HIV-positive individuals in particular, a novel source of organs is desperately needed. Organs from HIV-positive deceased donors (HIVDD) are a unique potential resource for HIV-positive individuals awaiting transplantation. By expanding the donor pool by potentially >2400 HIVDD annually, the use of HIVDD could also decrease the wait time for HIV-negative individuals, resulting in a far-reaching public health impact. Recognition of this need led to the passage of the HIV Organ Policy Equity (HOPE) Act by Congress and signed by President Obama, calling for research on HIV-to-HIV organ transplants. However, critical questions remain surrounding the use of HIVDD. With the support of the United Network of Organ Sharing (UNOS) and the Association of Organ Procurement Organizations (AOPO), we aim to define the epidemiology and HIV-specific biology of the HIVDD pool. Leveraging the existing infrastructure of UNOS and the OPOs, we will perform a comprehensive evaluation of potential HIVDDs and their recipients. First, we will define the size of the HIVDD pool and the distribution of demographic factors, comorbidities, HIV viral load, CD4 count, and use of antiretroviral therapy (ART) using rapid screens that are standard in deceased donor evaluation. Second, we will perform more time-intensive assays to determine the prevalence of potential contraindications to donation, such as extensive ART resistance, that cannot be assessed during the rapid screening window. Third, we will explore prediction models to determine whether rapid screening can estimate the risk of potential HIV-specific contraindications to donation. Finally, we will evaluate HIV-to HIV transplant recipient safety through a prospective observational study of HIV-to-HIV renal transplantation and also through mandated data collection by the Scientific Registry for Transplant Recipients. Understanding the HIVDD pool is critical for clinical decision-making (i.e. assessing individual risk) and for policy-making (i.e. whether it is safe enough to merit the use o some, or even all, HIVDD). We have assembled a team led by an early stage investigator with expertise in HIV epidemiology, laboratory testing, and leading multidisciplinary studies, a well-respected transplant surgeon with experience influencing national policy, researchers in basic HIV biology from Johns Hopkins and the NIH, an industry leader in diagnostic virology, AOPO, and UNOS. The HOPE Act directs the Secretary of HHS to develop guidelines for research related to HIVDD organ transplantation. Our study will provide critical information that can be immediately used to address this mandate. If the use of HIVDD can be safely implemented, thousands of lives of HIV-positive and HIV-negative individuals can be saved with potentially the largest expansion of the organ donor pool in the last decade.