September 2021 DAIDS Council-Approved Concepts

Concepts represent early planning stages for program announcements, requests for applications, notices of special interest, or solicitations for Council's input. If NIAID publishes an initiative from one of these concepts, we link to it below. To find initiatives, go to Opportunities & Announcements.

NB: Council approval does not guarantee that a concept will become an initiative.

Table of Contents

Fiscal Year (FY) 2023 Concepts

Limited Interaction Targeted Epidemiology: Viral Suppression (LITE-VS)

Request for Applications—proposed FY 2023 initiative

Contact
Gerald Sharp
gerald.sharp@nih.gov

Objective: The main objective of the LITE-VS initiative is to enroll large, electronically generated cohorts of people living with HIV-1 (PLWH) in the United States and follow participants who are not virally suppressed over time to prospectively investigate the predictors and mediators of viral suppression. Researchers may apply that knowledge to test strategies (e.g., social media tools, game theory, or other technologies) to provide information on ways to achieve consistent and stable viral suppression.

Description: LITE-VS will build upon previous successful approaches to enroll and retain large (i.e., > 1,000 participants) electronic cohorts in the United States. LITE-VS will focus on PLWH of all ages, sexes, and genders who are not consistently viral suppressed, with a requirement that at least 50 percent of participants have minority status. Investigators will be expected to enroll cohorts in the first two years of the award and meet negotiated milestones in terms of total, minority, and adolescent enrollment of non-suppressed PLWH in the United States. Grantees meeting milestones in the first two years of the award will be eligible to transition to the second phase and receive up to three additional years of funding. In Phase 2, awardees may conduct epidemiologic research comparing suppressed and non-suppressed participants, investigate the predictors and mediators of viral suppression over time, and, optionally, address methodological questions about how best to enroll and retain participants or to pilot digital interventions designed to improve levels of suppression.

Enhancing HIV Reservoir Susceptibility to Elimination

Request for Applications—proposed FY 2023 initiative

Contact
Diane Lawrence
diane.lawrence2@nih.gov

Objective: The objectives of this initiative are to 1) elucidate cellular and molecular mechanisms within persistently infected HIV reservoir cells that impact their susceptibility to death, 2) identify novel therapeutic targets within persistently infected cells that will increase their sensitivity to cell death, and 3) explore synergistic approaches to combine enhancement of cell death with latency reversal and/or immunotherapeutic strategies. These studies will inform efforts to develop more effective interventions for an HIV cure.

Description: This initiative will support basic research focused on understanding why some HIV reservoir cells are resistant to virus- or immune-mediated cell death despite potent reactivation and specific immunologic responses. It will also support translational research to sensitize these cells to death or killing, either by the immune system or by therapeutic interventions. Examples of research include but are not limited to: 

  • Defining the contribution of apoptosis pathways to survival, longevity, or expansion of blood and tissue HIV reservoirs
  • Approaches to counteract downregulation of MHC or impaired HIV antigen presentation
  • Identifying factors in the cellular microenvironment that inhibit reservoir elimination
  • Therapeutic strategies to test mechanistic hypotheses
  • Preclinical animal studies

The following would not be supported by this initiative

  • Studies focused primarily on improving latency reactivation or enhancing effector cell killing
  • Studies that do not extend to primary cells from HIV/SIV-infected hosts
  • Approaches that bypass cellular mechanisms, such as immunotoxins
  • Clinical trials (although use of samples from clinical studies and trials supported elsewhere would be encouraged)

Molecular Dynamics of HIV

Request for Applications—proposed FY 2023 initiative

Contact
David McDonald
david.mcdonald@nih.gov

Objective: This initiative will support computational dynamic modeling of molecular complexes regulating the HIV life cycle, immune responses, and therapeutic interventions using existing and new HIV/host structural datasets. Addition of the dimension of time to the three-dimensional structures already studied by structural biologists is expected to facilitate novel insights into their function. Research teams are expected to include computational modelers with structural biologists, virologists, immunologists, and other appropriate expertise to validate model systems.

Description

  • Molecular dynamics (MD) simulates the movement of atoms and molecules over time, providing testable models of complex molecular behavior. This initiative will support innovative structural, computational, and functional approaches to study the dynamics of molecular processes in the HIV life cycle.
  • The initiative will leverage the growing number of high-resolution HIV/host cell biomolecular structures by directly funding MD simulation research and incentivizing computational specialists to collaborate with HIV researchers.
  • Research teams should include structural dynamics modelers along with appropriate structural, virologic, immunologic, and/or cell biological expertise.
  • Projects should address a critical component of the HIV life cycle, antibody response, or therapeutic intervention that is amenable to structural determination and dynamic modeling.

Example research foci:

  • HIV capsid interactions with cytoplasmic and nuclear transport machinery
  • HIV transcription, latency, and epigenetic regulation
  • HIV assembly, budding, and release
  • HIV capsid maturation
  • HIV/host lipid interactions
  • HIV recognition by and escape from innate immune factors
  • Binding of neutralizing antibodies to HIV envelope proteins
  • Binding of HIV antigens to B-cell surface immunoglobulin receptors
  • Mechanisms of action of novel anti-HIV therapeutics and their interactions with host or viral targets

Examples of research that would not be supported through this initiative:

  • Applications that are not primarily focused on dynamic modeling of HIV/host structural data relevant to NIAID HIV research priorities
  • Applications that involve only theoretical modeling (e.g., based on amino acid sequences alone) without known molecular structures as starting points
  • Applications that do not include functional analyses of the modeling simulations
  • Applications that propose a clinical trial

A Multi-omics Approach to Immune Responses in HIV Vaccination and Intervention

Request for Applications—proposed FY 2023 initiative

Contact
Amy Palin
amy.palin@nih.gov

Objective: The objective of this initiative is the integration of bioinformatics and hypothesis-driven experimental approaches to define signatures of outcomes of HIV/SIV vaccination or intervention. New advances in high-throughput “omics” technologies have enabled profiling human immunity with great precision. The HIV field can leverage these systems-based approaches to analyze the immune response to infection, vaccines, therapeutics, or cure interventions in humans or animal models. The resulting high-throughput data can then be mined computationally to generate novel hypotheses about the underlying biological mechanisms, which can in turn be tested in animal or ex vivo models. The insights gained can then guide the design of new therapeutics and vaccines. This iterative cycle framework will bridge basic and applied science, as well as animal and human immunology, for scientific discovery and translational medicine.

Description: This initiative will support projects focused on an integrated, iterative approach to define molecular signatures predictive of outcomes in response to HIV immunization, therapies, or other interventions. Goals include development of improved vaccines, antibodies, therapies, and other immunomodulatory preventative, therapeutic, and cure interventions for HIV; mechanistic insights about the factors that lead to variation in outcomes; and engaging computational biologists to the HIV field. Molecular signatures found in samples from clinical trials and animal models will support hypothesis generation and validation. Both wet lab and computational components will be required. Clinical trials are not allowed but use of data and samples from clinical trials funded through other mechanisms is encouraged. Animal models, including nonhuman primates, are allowed. Integration of human and animal approaches is highly encouraged.

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