Basic Research in HIV and Substance Use Disorder

Presentation from the NIDA HIV Research Program: Substance use and HIV latency

Dr. Karn
Dr. Jonathan Karn, Case Western Reserve University

Mark your calendars for Wednesday April 26th, 1-2 pm ET for this unique opportunity to interact with a leading researcher at the intersection of HIV and substance use. The NIDA HIV Research Program (HRP) is pleased to announce the next presentation in its Seminar Series: A vicious cycle: The impact of inflammation and substance use on the control of HIV latency in microglia by Dr. Jonathan Karn, Reinberger Professor & Chair of the Department of Molecular Biology & Microbiology at Case Western Reserve University School of Medicine. Dr. Karn has been studying transcriptional control in HIV since the mid-1980s. His current research focuses on the impact of substance use on the regulation of HIV transcription and latency in microglial cells.

Highlighted Paper

  • Binding Mode of Human Norepinephrine Transporter Interacting with HIV‑1 Tat Adeniran C, Yuan Y, Davis SE, Lin C, Xu J, Zhu J, and Zhan C-G. ACS Chem. Neurosci. 2021, 12, 1519−1527
    The authors used computational approaches to model the molecular dynamics of the HIV-1 Tat interaction with the human norepinephrine transporter (hNET). This computational modeling provides insights that will inspire future pharmacological and biochemical studies of the interaction of HIV-1 Tat with hNET.

The Division supports research on the intersection of HIV and substance use disorders. This research cuts across all four scientific branches. Drug use is not only a vector for the entry of the virus into the circulation, but it can also facilitate brain entry by affecting blood brain barrier permeability.  Additionally, it is associated with risk-taking behavior that increases vulnerability to HIV and other infections. Importantly, substance use can contribute to the course of the disease through independent effects on immune function, by affecting cells that serve as reservoirs of the virus in the brain and through epigenetic mechanisms that regulate latency. Although HIV and addictive drugs can have independent effects on cell biology that contribute to brain diseases, the combination of HIV and drug use can have unique consequences that affect processes such as pain, neurocognitive function and aging. The basic research supported by the DNB provides opportunities to illuminate HIV biology and CNS biology and may provide potential avenues for treating the co-occurrence of HIV and substance use disorder.

Avenir Award in HIV/AIDS

NIDA’s Avenir Awards provide grants to early-stage investigators who propose highly innovative studies.  “Avenir” is the French word for “future”, and these awards represent NIDA’s commitment to supporting researchers who represent the future of addiction science. Awardees receive up to $300,000 per year for five years to support their projects. NIDA has two Avenir award programs, one for HIV/AIDS and another on the genetics and epigenetics of substance use disorders.

Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1)

The Avant-Garde Award is part of the Director’s Pioneer Award mechanism at NIDA that supports investigators with exceptional creativity proposing high impact research projects that will open new areas of HIV/AIDS research relevant to substance use disorders (SUD) and lead to novel avenues for prevention and treatment of HIV/AIDS among people who use drugs (PWUD).

Current Areas of HIV Research include:

  • Mechanisms of HIV latency formation and maintenance and effects of drugs of abuse
  • Role of Inflammasomes in HIV biology
  • Single cell brain responses to addictive drugs in the context of HIV (SCORCH Program)
  • Cannabinoid interactions with HIV biology
  • Use of iPSCs, organoids and/or gene editing technology to study HIV latency and pathology
  • Role of non-neuronal cells and HIV biology
  • Imaging HIV related processes in context of substance use disorder
  • Use of omics approaches to study HIV/drug interactions
  • Effect of HIV and addictive substances on brain epigenomic and non-coding RNA regulation
  • Antiretroviral therapy and addictive substances on cognitive function
  • Biomarkers-markers of HIV latency in the brain
  • Data science and computational approaches to study HIV-substance use dynamics
  • Formulations of ART to improve treatment and compliance

Funding Announcements

  • RFA-DA-21-026 - Using Human Cell Animal Chimera Brains to Study HIV Latency and Pathology (R01 - Clinical Trials Not Allowed)
  • RFA-DA-21-019 - Single Cell Opioid Responses in the Context of HIV (SCORCH) Program Expansion: CNS Data Generation for Chronic Opioid, Methamphetamine, and/or Cocaine Exposures (U01 Clinical Trial Not Allowed)
  • RFA-DA-21-013 - Advancing HIV/AIDS Research through Computational Neuroscience (R01 - Clinical Trial Optional)
  • RFA-DA-21-005 - Exploiting in vivo or in situ imaging approaches to understand HIV-relevant processes in the context of substance use disorders (R61/R33 Clinical Trials Optional)
  • PA-20-151 - Eradication of HIV-1 from Central Nervous System Reservoirs (R01 Clinical Trial Not Allowed)
  • PAR-DA-20-221 - NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1, Clinical Trial Optional)
  • PAR-DA-20-224 - Avenir Award Program for Research on Substance Use Disorders and HIV/AIDS (DP2 Clinical Trial Optional)