CROI 2025 Abstract eBook

Abstract eBook

Invited Session

INVITED SESSION PRESENTATION SUMMARIES

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Session Overview for the Scott M. Hammer Workshop for New Investigators and Trainees Katharine Bar 1 , Raphael J. Landovitz 2 , Serena S. Spudich 3 , Stuart J.D. Neil 4 , Lishomwa Ndhlovu 5 , Susan P. Buchbinder 6 , Judith S. Currier 2 , Joseph J. Eron 7 1 University of Pennsylvania, Philadelphia, PA, USA, 2 University of Los Angeles, Los Angeles, CA, USA, 3 ,Yale University, New Haven, CT, USA, 4 King's College London, London, UK, 5 Weill Cornell Medicine, New York, NY, USA, 6 San Francisco Department of Public Health, San Francisco, CA, USA, 7 University of North Carolina Chapel Hill, Chapel Hill, NC, USA Background: Over the past four decades, remarkable progress has been made in understanding HIV epidemiology, pathogenesis, treatment, and prevention from the combined efforts of community members, clinicians, investigators, and funding agencies worldwide. Yet more work and new approaches are needed to achieve the ambitious goal of ending the epidemic and ensuring optimal quality of life for those living with HIV. To encourage and stimulate the next generation of investigators, the CROI Program Committee organizes the Scott M. Hammer Workshop for New Investigators and Trainees comprised of expert and comprehensible talks to introduce key topics in basic, clinical, and public health investigation into HIV and related infections and to highlight relevant work to be presented over the ensuing days at CROI. This year, each presentation is preceded by a “Hearing Community Voices” testimonial focused on how the type of work impacts the community and how the community can impact the research. In the first talk, Stuart J. D. Neil will provide an accessible updated on Virology, and Lishomwa Ndhlovu will follow with a talk on Immunology. Susan P. Buchbinder will focus on the Prevention of HIV and STIs, followed by Judith S. Currier on Cardiovascular Complications of HIV. The session will end with a talk on HIV Cure Research by Joseph J. Eron, Jr. By completing the workshop, attendees will have achieved a head start toward maximizing the knowledge gained and research ideas as they navigate CROI 2025. Breaking the HIV Capsid: Atomic Force Microscopy Visualization Juan Perilla University of Delaware, Newark, DE, USA Background: The genetic material of HIV-1 is packaged inside a cone shaped container that is called the viral core. To infect a cell, the viral core must pass through the cell’s nuclear pore. Using atomic force microscopy, a technique that uses a tiny needle to feel the surface of things at the microscopic level, and molecular dynamic simulations, we discovered that wild-type HIV-1 cores quickly revert to their normal shape after compression, while capsid mutants with impaired nuclear entry are brittle. Restoring elasticity in these mutants recovered their ability to infect. Treatment with capsid-targeting drugs also reduced core elasticity. These findings suggest that capsid elasticity is essential for HIV-1 nuclear entry and infection, offering new insights into HIV-1 mechanics and potential antiviral strategies. Advances in Single-Cell Multiomic Profiling and Its Use in Virology and Immunology Alexander Marson University of California San Francisco, San Francisco, CA, USA Background: We use the power of CRISPR-based gene editing technologies to decode and rewrite DNA programs that govern cells in the human immune system. Human immune cells, especially T cells, can be genetically engineered to target various cancers. Despite their utility for the treatment of hematological malignancies, chimeric antigen receptor (CAR) T cells have significant limitations, which are especially clear in the context of solid tumors. Mounting evidence suggests that for many clinical applications, engineering the T cell to recognize the target cancer cells will not be sufficient to cure disease. Major challenges to the utility of immunotherapy in cancer include overcoming immunosuppressive tumor microenvironments and maintaining the therapeutic cells’ functionality in the tumor over time. We are working to accelerate the design of genome modifications and synthetic DNA sequences that can be

introduced into human T cells to program the enhanced functionality necessary to overcome these challenges.

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Visualizing Tissues: State-of-the-Art Single-Cell 3D Spatial Transcriptomics Nikolaus Rajewsky Berlin Institute for Medical Systems Biology, Berlin, Germany Background

Invited Session

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Advances in CRISPR-Cas Editing Methods and Their Use in Virology and Immunology Angela Wahl University of Alabama at Birmingham, Birmingham, AL, USA Background: Humanized mouse models, immunodeficient mice transplanted with human cells/tissues, have been used by HIV researchers for over 30 years to study aspects of HIV infection (e.g. transmission, pathogenesis, and persistence) and to perform efficacy testing of novel prevention, treatment, and cure approaches. This presentation will introduce the most commonly used humanized mouse models for HIV research providing details on their construction, reconstitution with different human cell types, susceptibility to different routes of HIV transmission, and parameters of infection. The application of humanized mice for testing novel antivirals, biologics, and cell and gene therapy approaches will also be discussed as will practical considerations for working with these models. This presentation will highlight strengths of using humanized mouse models for HIV research, challenges, and areas for further refinement. A future outlook on the use of humanized mice for HIV research will also be provided. Background: This case-based session will address the most common cause of liver disease namely metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), and the overlapping entity MetALD. The audience will become familiar with the new nomenclature, epidemiology, clinical diagnosis, and risk-stratification using non-invasive tests. In addition, practical approaches to MASLD treatment including newly approved medications will be discussed. Join this session to: (1) gain insights into the spectrum of steatotic liver disease and (2) enhance knowledge of MASLD diagnostic and new therapeutic strategies in clinical practice. Liver Steatosis: New Nomenclature, New Tests, and New Drugs Mandana Khalili University of California San Francisco, San Francisco, CA, USA

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CROI 2025