Funding Opportunity Number: RFA-DA-26-009
Deadlines
Letter of Intent: February 10, 2025
Submission: March 10, 2025
Background
According to the Centers for Disease Control and Prevention, more than half of all people with human immunodeficiency virus (HIV) in the United States are age 50 or older, and thousands of older people acquire HIV every year. The lifelong consequences of living with HIV, heritage antiretroviral therapies (ART) and/or use of addictive substances remain understudied and are independently associated with interrelated mechanisms that contribute to aging such as epigenetic regulation gene expression, mitochondria damage/stress, inflammation, and cell death.
This notice of funding opportunity (NOFO) invites applications to investigate protective and pathogenic mechanisms at the nexus of mitochondrial function and aging in the context of HIV infection, ART and exposure to addictive substances. Basic and preclinical research projects are appropriate. Substances of interest include, but not limited to: synthetic and non-synthetic opioids, nicotine, cocaine, methamphetamine, other stimulants, psychedelics, xylazine, addictive prescription drugs, cannabinoids, or combinations of these substances. We anticipate this foundational knowledge could be leveraged to develop targeted therapies and improve outcomes in people aging with HIV, substance use and addiction.
Research areas that are pertinent to this NOFO include, but are not limited to:
- Elucidate how changes in mitochondrial dynamics, function, metabolomics and stress response contribute to accelerated aging and maintenance of viral reservoirs in people living with HIV and SUDs.
- Determine targetable mechanisms to alleviate mitochondria stress to prevent or improve outcomes in people living with or at risk for HIV and SUDs.
- Characterize mitochondrial regulation of activation and senescence in different types of neural and immune cells by HIV status, ART, substances used (including polypharmacy), duration of substance use, and age. Measures of mitochondrial function and dynamics may include gene expression, signaling, types of mutations and mutation rate, oxidative stress and oxidative damage, fission/fusion states and mitophagy, etc.
- Determine how mitochondrial haplotypes, somatic mutations in nuclear DNA and mitochondrial DNA contribute to neurocognitive impairment and SUD as people living with HIV age.
- Elucidate which areas of the mitochondrial and nuclear genomes are damaged during HIV and use of addictive substances by associated oxidative stress, and how their epigenomes, transcriptomes, and gene regulatory pathways differ. Determine how these modifications contribute to neuropathogenesis.
- Development of computational models for mitochondrial dysfunction to identify those at risk for pathological aging in people living with HIV and SUD.
For more information, please see the opportunity webpage.