This Notice of Funding Opportunity (NOFO) seeks to stimulate HIV/AIDS research within the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that align with the HIV/AIDS research priorities outlined by the NIH Office of AIDS Research (OAR). These priorities were most recently described in NOT-OD-20-018 UPDATE: NIH HIV/AIDS Research Priorities and Guidelines for Determining HIV/AIDS Funding. Systemic complications of HIV directly affect many of the organ systems and processes within the research mission of the NIDDK. Diseases and conditions within NIDDK's mission include diabetes and other endocrine and metabolic diseases; gastrointestinal, liver, and pancreatic diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases. NIDDK has many research areas within its mission, but all research related to relevant diseases may not be appropriate for NIDDK. Applicants are strongly encouraged to contact NIDDK staff as soon as possible in the development of the application, so that NIDDK staff can help the applicant understand whether the proposed project is within the goals and mission of the Institute. In addition, NIDDK-relevant organs and tissues play central roles in HIV establishment, spread, persistence, and transmission.

Several HIV-related comorbidities, co-infections, and complications (CCCs) within NIDDK's mission are prevalent in people with HIV (PWH). Important problems include enteropathy and loss of gastrointestinal homeostasis; noncommunicable liver diseases and viral hepatitis co-infections; kidney, urologic, and hematologic diseases; and obesity, diabetes, and associated complications. Moreover, NIDDK-relevant pathogenic processes may contribute to HIV pathogenesis in other tissues and organ systems. For example, loss of intestinal epithelial barrier function in HIV-associated enteropathy may result in systemic inflammation that contributes to the development of chronic diseases and conditions, including obesity or liver disease. Likewise, obesity can contribute to the development of diabetes or kidney disease. Mechanistic interrogation of the processes whereby HIV or its treatment contributes to these CCCs is needed to identify and develop strategies for both prevention and treatment.

Several tissues within NIDDK’s mission represent important HIV reservoirs. These include the gastrointestinal mucosa, the male genital tract, the kidney, and adipose tissue. Mechanistic interrogation of HIV reservoirs in different tissues is the pivotal step toward achieving HIV cure. The dynamics of different reservoirs often have unique aspects. Therefore, basic and translational research into the specific mechanisms impacting reservoirs within NIDDK’s mission is central to development of strategies toward achieving sustained antiretroviral therapy-free viral remission or eradication from the body.

Topics within the scope of NIDDK's mission often cut across priority HIV/AIDS research areas. These include fundamental studies of the gastrointestinal and penile microbiomes or gastrointestinal and penile mucosal immunology that may be important to our understanding of CCCs, viral reservoirs, or other priority NIH HIV/AIDS research.

Health-impeding social determinants of health (SDoH) play a significant role in the development of HIV-related CCCs within the scope of the NIDDK’s mission. Examples include food insecurity, poor nutrition and its sequelae, homophobia, transphobia, racism/discrimination, financial resource strain, stigma associated with both HIV and with the co-occuring chronic condition, inadequate housing, and lack of access to health care and resources, among others. The downstream effects of these SDoH impede patient engagement related to health-promoting and self-managing behavior and act as barriers to completing necessary tests, procedures and treatments. Moreover, there may be biological consequences. For example, nutritional inadequacies resulting from food insecurity and heightened stress/allostatic load may impact physiological or pathophysiological processes leading to the development of obesity, liver disease, or kidney disease. Given that CCCs might impact viral reservoirs, health-impeding SDoH could also have consequences on reservoir dynamics and cure strategies. Furthering our understanding of how SDoH contribute to HIV-related CCCs is essential to implementing effective and comprehensive prevention programs.