Funding Opportunity Number: RFA-DA-25-073
Deadlines
Letter of Intent: July 14, 2025
Submission: August 14, 2025
Background
Despite the impressive success of antiretroviral therapy (ART) in reducing HIV-1 associated mortality, ART is unable to fully eliminate latent HIV reservoirs in patients, including in the central nervous system (CNS). There is much that remains to be understood regarding the establishment and persistence of the latent CNS reservoir as well as the effects of inflammation, ART, or the blood brain barrier on this reservoir or on HIV pathogenesis in the CNS. As an added layer of complexity, addictive substances have the potential to impact HIV infection, establishment and maintenance of latency, and/or disease progression including inflammation and neuroHIV. For example, chronic exposure to addictive substances may disrupt blood brain barrier permeability, which could impact viral CNS entry. Addictive substances may also influence the establishment or maintenance of HIV latency of the CNS or alter systemic or localized inflammation which could impact HIV disease progression. Individuals with substance use disorders (SUDs) may have decreased adherence to ART medications which may impact CNS viral replication or latency. It is critical to unravel the complex interactions between HIV disease, ART, and addictive substances in order to understand and treat HIV in individuals with SUDs. Exploratory studies are needed to develop or apply novel tools or technologies or to test novel hypotheses in order to obtain a deeper understanding of the mechanistic interactions between HIV disease, ART, SUDs, and SUD therapies.
Research Objectives
The purpose of this notice of funding opportunity (NOFO) is to support milestone-driven preclinical research that will propose to test a novel or out-of-the-box hypothesis to advance the HIV/SUD research area. This initiative focuses on exploration and characterization of biological mechanisms and/or signaling processes that are involved in CNS HIV establishment and expansion.
To be considered responsive, all applications must include the components listed below. Applications deemed non-responsive to this RFA will be withdrawn without review:
- The major thrust of the project MUST propose compelling studies to investigate mechanisms of HIV infection, replication, latency, and/or pathogenesis or the effects of ART on these processes.
- At least one aim MUST also involve either (1) opioid, cannabinoid, nicotinic, dopaminergic, or other signaling pathways relevant to addictive substance use, or (2) exposure to addictive substances, or (3) analysis of samples from patients that have used addictive substances or have SUDs. Substances of interest include: nicotine, cocaine, methamphetamine, stimulants, opioids, addictive prescription drugs, cannabinoids, combinations of these drugs, or combinations of these drugs with alcohol. Applications proposed to study HIV but focused solely on alcohol exposure will be considered non-responsive to this NOFO. Studies proposing long term exposure to addictive substances are encouraged.
- The proposed project MUST focus on brain OR well-justified studies using blood, or lymphoid systems or on tissues or cells relevant to these systems. Proposed projects using tissues or cells relevant to cardiac, kidney, liver, or lung systems will be considered non-responsive.
- The proposed project MUST include one aim or sub-aim investigating humans or primates, animals with humanized immune systems and/or cells (including organoids) derived from human or primates.
For more information, please see the opportunity webpage.