Scrutinize Molecular Mechanisms Amid Suppressive Antiretroviral Therapy

Funding News Edition: April 19, 2023
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What are the molecular mechanisms by which HIV proteins and nucleic acids induce inflammation, immune activation, and HIV persistence during viral suppression? Could novel therapeutic strategies mitigate or eliminate the effects of continued HIV expression? If you can conduct the research needed to answer these questions, consider applying for support through NIAID’s notice of funding opportunity (NOFO) Defining Mechanisms of HIV-Induced Inflammation and Immune Activation During Suppressive Antiretroviral Therapy (ART) (R01, Clinical Trial Not Allowed).

Through this NOFO, NIAID aims to spur new approaches that target HIV transcription to shut down the expression of HIV RNA, proteins, and virus that occurs despite interruption of the viral life cycle by ART. Understanding the pathways and mechanisms induced by these viral products, as well as their impact on HIV persistence and rebound, could result in novel strategies to reduce the downstream chronic health complications of individuals infected with HIV.

Consider the following examples of research responsive to this initiative:

  • Single-cell approaches to define the HIV RNA and protein landscape in different cellular subpopulations harboring intact and defective provirus in the context of ART.
  • Identifying mechanisms and pathways where HIV RNA and proteins expressed under ART lead to loss of immune regulation or homeostasis.
  • Strategies to inhibit HIV expression or alter pathways to reduce HIV-induced inflammation, immune activation, and exhaustion, e.g., developing novel drugs that block HIV-1 transcription, Tat-mediated transcriptional elongation, or newly identified pathways.
  • Strategies that target HIV transcription to prevent expression of HIV proteins and nucleic acids during suppression by ART.

To be clear, the above list is not exhaustive. You may propose other types of studies to meet the aims of the NOFO.

However, NIAID will consider your application nonresponsive and not review it should you propose any of the following:

  • Identifying cellular biomarkers which are elevated during HIV-induced inflammation.
  • Therapeutic strategies which target cellular biomarkers (inflammation).
  • Studies focused on pathways involving the microbiome.
  • Clinical trials (refer to NIH’s Definition of a Clinical Trial).

Additionally, animal studies can include only small animal models (i.e., humanized mice) for proof-of-concept studies.

Your application budget is not limited but must reflect the actual needs of the proposed project. The project period cannot exceed five years.

This NOFO has a single application due date: August 2, 2023, at 5 p.m. Eastern Time of the applicant organization.

Direct questions about the NOFO to NIAID’s scientific/research contact Dr. Gerard Lacourciere at or 301-761-7477. For matters related to peer review, instead contact Dr. Lee Klinkenberg at or 301-761-7749

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