The purpose of this Notice of Special Interest (NOSI) is to continue advancing our understanding of the risks, development, progression, diagnosis, and treatment of malignancies observed in individuals with an underlying human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), particularly the non-AIDS defining malignancies which are now a leading cause of death in HIV-infected individuals. Research efforts that identify specific contributions of HIV infection and its potential interaction with other pathogens towards the development and pathogenesis of these cancers and provide information on the clinical outcomes of such cancers in the HIV-infected population are sought. Ultimately, such efforts could inform screening approaches and therapies targeted to the HIV-infected population.

High or medium priority AIDS research as described in NOT-OD-15-137 is encouraged in areas such as the study of the etiologic factors, cofactors, immunopathogenesis, diagnosis, and consequences of both non-AIDS defining and AIDS-defining malignancies in populations with an underlying HIV infection.

Background

Past and current progress in the development of treatments and understanding the molecular mechanisms of Acquired Immune Deficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) infection has greatly improved patient survival. However, increased survival has been accompanied by the development of cancer at a higher rate in treated individuals than that observed in the HIV/AIDS negative population. During the early days of the AIDS epidemic the most frequently reported AIDS-defining malignancies were Kaposi’s sarcoma (KS) and Non-Hodgkin lymphoma (NHL). Now with increased survival as a result of widespread use of antiretroviral therapy (ART), non-AIDS defining cancers (i.e., anal, skin, and lung cancers, and Hodgkin’s disease) are on the increase in HIV infected populations.

The topics chosen for this NOSI are aligned with relevant areas of emphasis described in the NIH Office of AIDS Research (OAR) FY 2019/2020 NIH Strategic Plan for HIV and HIV-Related Research. As a priority area, the 2019/2020 NIH Plan includes the need to address HIV-Associated Comorbidities, Coinfections, and Complications. Assessing the impact of malignancies and understanding their pathogenesis in HIV-infected patients is of high priority.

Research Objectives

NCI continues to seek research that advances our understanding of the risks, development, progression, diagnosis, and treatment of malignancies observed in individuals with an underlying HIV infection. Research that addresses high or medium priority AIDS research in areas such as etiologic factors, coinfections, cofactors, immunopathogenesis, diagnosis, and consequences of both non-AIDS defining and AIDS-defining malignancies in populations with an underlying HIV infection is sought in response to this NOSI.

Note: Topics considered low priority AIDS in NOT-OD-15-137 are not appropriate for this NOSI. Basic research in tumors caused by KSHV is, for the moment, being considered as high priority AIDS and will be eligible for funding under this NOSI. All applications considered for funding will be reviewed by OAR and must be aligned with the priorities in NOT-OD-15-137.

This NOSI encourages, but is not limited to, research applications in the following areas:

• Etiology, Pathogenesis and Immunology
  • Studies to determine pathogenic or immune response mechanisms of infectious agents that interact with HIV, mediate tumor initiation and promotion of malignancies;
  • Studies of how aging processes and HIV interact in the development of either non-AIDS-defining or AIDS-defining malignancies;
  • Development of animal and/or cell-based models for non-AIDS-defining and AIDS-defining malignancies with an underlying HIV infection;
  • Studies to determine the cellular epigenome, proteome, glycobiome, and transcriptome of tumors in the context of HIV infection;
  • Studies investigating HIV-associated alteration of the microbiome and its impact on non-AIDS-defining and AIDS-defining malignancies.
• Biomarkers, Diagnostics, and Therapeutics
  • Discovery of reliable molecular and immunological diagnostic and prognostic biomarkers and pathogen markers, useful for early detection, progression, or response to treatment of non-AIDS-defining and AIDS-defining malignancies;
  • Studies utilizing existing cohorts and tissue banks of human specimens from a wide spectrum of AIDS-defining and non-AIDS defining malignancies to develop biomarkers, diagnostic assays, or analyze samples and data acquired from these cohorts is encouraged. Examples of such cohorts and repositories include:
    • AIDS and Cancer Specimen Resource (ACSR),
    • MACS/WIHS Combined Cohort Study (MWCCS)
    • Veterans Aging Cohort Study (VACS)
    • International epidemiology Databases to Evaluate AIDS
• Molecular Epidemiology and Prevention
  • Determine the relationship of omics data to the natural history of non-AIDS-defining or AIDS-defining malignancies;
  • Studies to characterize the immunologic, virologic, genetic, and epigenetic differences between those patients on ART who develop pre-neoplastic and neoplastic conditions and those patients who resolve these conditions or do not develop them;
  • Studies to characterize the host genetic susceptibility to non-AIDS-defining and AIDS-defining malignancies in the context of HIV infection;
  • Assessment of risk factors (e.g., tobacco, infections, diet, and nutrition) that impact cancer in the context of HIV infection, in different geographic locations in domestic and international settings.

Application and Submission Information

This notice applies to due dates on or after May 7, 2020, and subsequent receipt dates through January 8, 2023.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice. Although the National Cancer Institute (NCI) is not listed as a Participating Organization in all the FOAs listed below, applications for this initiative will be accepted.

• PA-19-056 -- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-19-053 -- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PAR-20-052 -- NCI Small Grants Program for Cancer Research for Years 2020, 2021, and 2022 (NCI Omnibus R03 Clinical Trial Optional)
• PAR-20-030 -- HIV-associated Non-Communicable Diseases Research at Low- and Middle-Income Country Institutions (R21 Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include "NOT-CA-20-022" (without quotation marks) in the Agency Routing Identifier field (box 4b) of the SF424 R&R form. Applications without this information in box 4b will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.