CROI 2025 Abstract eBook

Conference on Retroviruses and Opportunistic Infections March 9-12 | San Francisco, California

Abstract eBook

Abstract eBook

Contents

CONTENTS

Contents

ABSTRACTPROCESS..................................................................................... 4

INVITEDSESSIONPRESENTATIONSUMMARIES.............................................................. 6

ORALABSTRACTS. ..................................................................................... 16

POSTERS ABSTRACTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

DISCLOSURE OF FINANCIAL RELATIONSHIPS WITH INELIGIBLE COMPANIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458

AUTHORINDEX....................................................................................... 459

SEARCH TERM INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483

Version 4 | Last Updated on April 18, 2025 ©- Copyright 2025 CROI Foundation/IAS–USA. All rights reserved. ISBN #978-1-7320053-9-6

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Abstract Process

ABSTRACT PROCESS

Scientific Categories B asic Science

For more information, visit the CROI Abstract Categories webpage. Note, abstracts that were submitted in categories designated with the letters C, S, U, and W were integrated into other categories. Example citation: Smith I, Jones RM, Peters S, et al. Randomized clinical trial in HIV infection [CROI Abstract 1450]. Abstracts From the 2025 Conference on Retroviruses and Opportunistic Infections. CROI 2025 Abstract eBook. 2025;601. Note: These abstracts were current at the time they were submitted, which may have been months before the start of CROI. For the most up-to-date data, please view the posters and oral abstract presentations on the conference app. To search for specific word or term, presenters, or authors on this document, hold the “Ctrl” and press the “F” keys on your keyboard to prompt a word search. CROI conference materials (including, but not limited to, the CROI Program Guide, Abstract eBook, electronic posters, CROI logo, etc) are protected by copyright. Permission to replicate or reproduce any part of CROI materials (such as an abstract as formatted in the CROI Abstract eBook) must be obtained from the CROI Conference Manager, the International Antiviral Society–USA (IAS–USA). However, study data are the property of the author(s) and study sponsors as relevant. For more information, please email CROIabstracts@iasusa.org. Abstract Numbering: Presentation summaries for invited sessions begin with abstract 1. Oral abstracts begin at abstract 100. Poster abstracts begin at 300. Abstract numbers 52 to 99 and 205 to 299 were intentionally omitted to accommodate this numbering. Similarly, abstracts that were withdrawn are marked as such next to their preserved number. Abstract Content Author names, institutions, titles, and abstracts in the CROI Program Guide, Abstract eBook, Conference App, and other materials are presented largely as provided by the submitting author. THE SUBMITTING AUTHOR IS RESPONSIBLE FOR ENSURING THAT ALL COAUTHORS HAVE REVIEWED AND APPROVED THE ABSTRACT before submission and for providing complete and accurate contact information for all authors, including email addresses.

Abstract Process

A. Virology of HIV, SARS-CoV-2, or MPXV B. Pathogenesis of HIV, SARS-CoV-2, or MPXV: Human Studies and Animal Models C. Host Immune Responses, Vaccines, and Immunotherapies: HIV, SARS-CoV-2, or MPXV D. HIV Reservoirs, Latency, and Cure E. Neuropathogenesis and Neurologic Complications of HIV and SARS-CoV-2 Infection and Neurologic Complications of HIV in Adults G. Antiviral Therapy: Pre-Clinical Data, Randomized Trials, Efficacy, and Effectiveness Studies in HIV or SARS-CoV-2 or MPXV in Adults H. Resistance of HIV or SARS-CoV-2 to Small Molecules and Antibodies in Adults I. Hepatitis Viruses and Liver Complications in Adults J. HIV-Related Malignancies and Tumor Viruses K. Cardiovascular Complications of HIV Infection and Antiretroviral Therapy L. Other Complications of HIV Infection and Antiretroviral Therapy in Adults M. Clinical Manifestations and Outcomes of SARS-CoV-2, Including Long COVID N. Tuberculosis and Other Opportunistic Infections, Including the Impact of HIV in Adults O. Maternal and Fetal HIV and SARS-CoV-2 P. Childhood and Adolescent HIV, SARS-CoV-2, or MPXV Epidemiology/Public Health Q. Epidemiology of HIV, COVID-19, and Mpox R. Testing for HIV, COVID-19, and Mpox in Adults: New Tests, Population Studies, and Scale-Up S. Prevention of HIV, COVID-19, and Mpox in Adults T. Contraception, Sexually Transmitted Infections, and Reproductive Health in Adults U. Implementation and Scale-Up of Prevention and Treatment Interventions for HIV, and Impact of COVID-19 and Mpox on HIV-Related Programs Clinical F. Clinical Pharmacology in Adults

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Abstract Processs

Requirements for Abstract Content Study Design: Presentations from randomized trials and cohorts should follow the ICMJE guidelines, including reporting of study designs (eg, prospective, observational, randomized, double-blind, STROBE, CONSORT, or others), statistical methods, and outcomes by demographic variables. Please also note whether the study is ongoing or completed and whether the results are preliminary or final. Figures and Tables: Figures, tables, or other illustrations that exceeded the abstract submission guidelines were removed from the submitted abstract and are not included in the Abstract eBook. For examples and for additional information on this review process, visit the Common Reasons for Removal webpage. New Compounds: For abstracts describing new compounds, the chemical or molecular structure must be shown in the presentation. It need not be part of the abstract or be published in the Abstract eBook. Sex and Gender: Appropriate information and correct terminology should be used with regard to sex and gender. For human clinical or epidemiologic studies, the presentation should provide sex stratified results or identify who was included if it only included only a single population. Appropriate terminology such as “cisgender” (people whose gender matches the sex assigned at birth) or “transgender” (people whose gender does not match the sex assigned at birth) should be used. Both sex and gender data should be provided in the presentation. Presentations of preclinical data, including the use of cell lines and animal studies should include the sex of the animals or the sex of the source of the cell lines. If data are not available on sex and gender, this should be identified as a limitation in your presentation. Person-First Language and Appropriate Terminology: CROI strongly advocates for the use of and strives to incorporate “people first” language and acceptable terminology in all CROI-related materials and presentations. All abstract authors and presenters should apply the following basic principles of appropriate language and terminology including: • Describe populations as “people, persons, or individuals with HIV” rather than “HIV-infected people, persons, or individuals.” • Do not characterize people by their disease, infection, or condition; instead, use “people who inject drugs,”“individuals with cirrhosis,” or other similar constructs. • Out of respect for their contributions to our scientific advances, do not describe people enrolled in research studies or clinical trials as “subjects” or “patients.” Acceptable terms include research study or clinical trial “participants” or “volunteers.”

• Do not use the term “sterilizing” when referring to HIV cure; it triggers a negative perception in many people due to historic sterilization campaigns and may discourage participation in research. Abstract Review Process For more information, visit the Abstract Guidelines and Submission webpage. Statistics for Abstracts General Abstracts Submitted ��������������������������������������������������������� 1875 General Abstracts Accepted ����������������������������������������������������������� 1170 Late-Breaking Abstracts Submitted ������������������������������������������������ 285 Late-Breaking Abstracts Accepted ����������������������������������������������������� 94 Total Abstracts Accepted ������������������������������������������������������������ 1070 Oral Abstract Presentations ����������������������������������������������������� 106 Themes Discussion Presentations ��������������������������������������������� 59 Poster Presentations ������������������������������������������������������������������� 1064 Accepted Abstracts for Emerging Infections or Specific Populations Adolescents ������������������������������������������������������������������������������������������� 74 Men who have sex with men (MSM) ����������������������������������������������� 159 People Who Inject Drugs (PWID) ������������������������������������������������������� 59 Transgender Men or Women ������������������������������������������������������������� 61 Women or girls ����������������������������������������������������������������������������������� 172

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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

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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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Hepatitis B in the Gray Zone: Personalizing Treatment and Monitoring Paul Kwo Stanford University, Stanford, CA, USA Background: Hepatitis B remains a significant cause of liver disease and remains the leading cause of hepatocellular carcinoma worldwide. Effective therapy for hepatitis B is available, and nucleos(t)ide analogs (NAs) suppress hepatitis B DNA levels and normalize ALT levels. Long-term treatment can lead to reduction in necroinflammatory activity, with potential improvement in fibrosis or reduction in fibrosis progression, as well as a reduction in the risk of hepatocellular carcinoma. Treatment recommendations are guided by the degree of inflammation as reflected by ALT levels, HBV DNA levels and the degree of fibrosis. Current societal guidelines have recommended treatment during certain phases of hepatitis B infection in those who are HBeAg+ or HBeAg- with elevated HBV DNA levels and intermittently or persistently elevated ALT levels. However, approximately 30% of individuals with chronic hepatitis B remain in the gray zone including both HBeAg+ and HBeAg – infected individuals where HBV DNA and ALT levels do not fit into these well-described phases. Recent cohort studies have suggested that patients within the gray zone remain at risk for significant fibrosis and development of hepatocellular carcinoma. One limitation of gray zone patients has been the lack of histologic assessment of inflammation and fibrosis, rather relying on ALT and non-invasive measures of fibrosis. One recent study identified 242 individuals with chronic HBV infection in the gray zone, of whom 73% had significant histological disease. More recent treatment recommendations have suggested lower thresholds for treatment. Given the effectiveness of NA therapy and the recent data demonstrating improved functional cure rates with emerging therapies, patients in the gray zone should be assessed for treatment to reduce the incidence of advanced fibrosis, disease progression, and hepatocellular carcinoma in this highly prevalent disease. New biomarkers and risk models are needed to more accurately identify patients with significant inflammation and fibrosis who reside in the gray zones and would benefit from antiviral treatment and surveillance for hepatocellular cancer. Regardless, close follow-up of hepatitis B patients is required, given the highly dynamic interplay between the virus and the host. Liver Cancer Surveillance: Who, How, When, and For How Long Fasiha Kanwal Baylor College of Medicine, Houston, TX, USA Background: Most liver cancer (also called hepatocellular cancer, or HCC) cases occur in patients with established risk factors for chronic liver disease, including hepatitis C virus (HCV) infection, heavy alcohol drinking, hepatitis B virus (HBV) infection, and metabolic dysfunction associated steatotic liver disease (MASLD). These HCC risk factors lead to cirrhosis, which is present in 90% of patients with HCC in the Western world. Two large randomized controlled trials in patients with HBV and several observational cohort studies in patients with cirrhosis have shown that patients who undergo HCC surveillance have earlier-stage HCC, are more likely to receive potentially curative treatment, and have improved survival than those who presented symptomatically or had HCC detected incidentally. Based on these data, professional societies recommend HCC surveillance every 6 months in at-risk individuals, including all patients with cirrhosis from any etiology and subgroups of patients with HBV in the absence of cirrhosis. Surveillance is not recommended in patients with Child–Pugh class C cirrhosis unless they are awaiting liver transplantation, given the low probability of treatment eligibility and limited benefits. Liver ultrasound has been long regarded as a standard surveillance test for HCC. Ultrasound is non-invasive and relatively inexpensive. However, the performance of ultrasound can be impacted by several patient-level factors, with particularly suboptimal performance in obese patients (such as those with MASLD) and those with more advanced cirrhosis. Addition of blood-based biomarkers to ultrasound increases the sensitivity of surveillance, particularly for early tumor detection. The best-studied biomarker to date is AFP, with a level of 20 ng/mL being the most used cutoff to trigger further evaluation in clinical practice. The pooled sensitivities of ultrasound with and without AFP for early-stage HCC are 63% (95% CI, 48%–75%) and 45% (95% CI, 30%–62%), respectively ( P = .002).

HCC surveillance should be performed every 6 months. Once initiated, there is no consensus about when to stop surveillance. In general, surveillance can be stopped in patients who develop child C cirrhosis and who are not liver transplant candidates. Despite demonstrated benefits, including early tumor detection, <20% of patients with cirrhosis undergo surveillance. Using Machine Learning to Focus HIV Prevention Interventions Carlos S. Saldana Emory University, Atlanta, GA, USA Background: This session explores the transformative impact of artificial intelligence (AI) across the HIV research continuum, from basic science to public health. Key highlights include AI's role in accelerating drug discovery, optimizing clinical trials, and enhancing HIV care and prevention strategies. Emphasis is placed on ethical considerations, community engagement, and implementation science to ensure equitable and effective integration of AI-driven innovations. The discussion aligns with the Ending the HIV Epidemic initiative, showcasing AI as a catalyst for precision medicine and public health advancements in the fight against HIV. HIV Prevention Efficacy Trial Design: Lessons From Recent Trials Holly Janes Fred Hutchinson Cancer Center, Seattle, WA, USA Background: I will overview the state of the art in HIV prevention efficacy trial design and articulate lessons learned from recently conducted trials. How Much Is Enough: The Importance of Pharmacokinetic Targets Paolo Denti University of Cape Town, Cape Town, South Africa Background: A pharmacokinetic (PK) target is a specific drug concentration range in the body that ensures maximum efficacy while minimizing toxicity. In HIV clinical trials, selecting the correct PK target is crucial for the success of the study and the interpretation of its results. This issue is particularly relevant when evaluating the treatment of understudied populations like pregnant women, children, or patients on treatments with potential drug-drug interactions, such as those for tuberculosis (TB). These studies are generally too small to assess efficacy and toxicity, but they rather aim to show that target concentrations are successfully achieved. This makes the choice of a suitable PK target even more crucial. This presentation emphasizes the importance of accurate and critical selection PK targets, highlighting the risks of relying on widely accepted values from literature, which are often based on surprisingly limited evidence. Case Presentation With Panel Discussion, Plus Questions and Answers From the Audience Pedro Cahn 1 , Jennifer F. Hoy 2 1 Fundación Huésped, Buenos Aires, Argentina, 2 Alfred Health, Melbourne, Australia Background: In this session, Drs. Pedro Cahn and Jenny Hoy will present cases to an expert faculty panel from around the world to highlight cutting-edge issues in the care of people with HIV. Topics will include the management of weight gain in the setting of ART, the approach to cardiovascular events in people with HIV, whether people who are elite controllers should be treated with ART, and ART considerations for people with drug-resistant HIV and adherence challenges. This stimulating interactive session will illustrate the current evidence-based approaches to managing people with HIV from different parts of the world. How Integration Site Analyses Inform HIV Pathogenesis, Persistence, and Gene Therapy Frederic Bushman University of Pennsylvania, Philadelphia, PA, USA Background: Studies of HIV DNA integration provide a rich example of how basic research can inform new therapies, and how findings from translational implementation in turn can pose new questions. To replicate, a retrovirus such as HIV must integrate a DNA copy of the viral RNA genome into host cells. Establishing methods for analyzing HIV DNA integration in vitro helped launch the development of the integrase inhibitors, a pivotal class of antiretroviral drugs. Coming from another direction, studies of HIV integration target site selection have provided additional insights into mechanisms of replication and control of viral replication. Early studies showed that HIV favors integration in active transcription units, which makes sense for facilitating efficient HIV gene

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expression after integration. Further studies showed that tethering to cellular chromatin binding proteins contributed to targeting. Recent studies in people with HIV who effectively control virus show that distributions may be enriched in regions where the virus is poorly expressed due to aggressive selection by CD8+ T cells. These results have been recapitulated in various cell culture and animal models, allowing detailed mechanistic analysis. Studies of integration targeting also inform monitoring of human gene therapy, where insertional mutagenesis by gene transfer vectors is a concern. Recent studies suggest that HIV and retroviral vectors can carry out insertional mutagenesis in humans via four different mechanisms: enhancer insertion, promoter insertion, gene inactivation, and gene activation by mRNA 3’ end substitution. Stepping back, these mechanistic studies provide an overview of how basic research advances treatment of HIV, and contribute to the conceptual foundation for addressing many other disorders. 40+ Years of HIV: What’s Changed, What Hasn’t, What Shouldn’t, What Must Rebecca Denison Woman Organized to Respond to Life-threatening Diseases (WORLD), Berkeley, CA, USA Background: We are gathering in a moment of tremendous challenges and opportunities. We have developed biomedical tools to prevent HIV transmission and support the wellbeing of over 38 million individuals living with HIV, yet a truly healthy world eludes us. Stigma, discrimination, preventable deaths, and inequitable access to resources and health care persist. Human rights that have progressed in some places are under attack in others. Across the U.S., and perhaps the world, we are more connected yet more lonely than ever before. Our greatest achievements in evidence-based science are undermined by misunderstandings and deliberate disinformation. While many young people in the U.S. have never heard of HIV, and many of their parents think “AIDS is over,” the internet offers newly diagnosed people a firehose of information at the expense of their privacy. Meanwhile, their elders — long-term and lifetime survivors — bear the weight of trauma, gratitude, and persistence in a world unprepared to meet the needs of people aging with HIV. The challenges we face call for creativity, collaboration, and courage. Please join 42-year HIV survivor Rebecca Denison — Bay Area writer, founder of WORLD, co-founder of ICW, and clinical research participant since 1985 — as she reflects on lessons from the past, challenges in the present, and opportunities for the future. When Science Alone is Not Enough: The Intersection of Drug Use, Public Health, and Policy Adeeba Kamarulzaman Monash University Malaysia, Kuala Lumpur, Malaysia Background: From the beginning of the pandemic, people who inject drugs (PWID) were identified as a key population at significant risk of HIV infection. However, despite evidence of the effectiveness of harm reduction, many countries failed to respond adequately or in a timely manner. Embedded in prohibition and punitive approaches, Malaysia’s initial resistance to harm reduction led to a large, concentrated epidemic amongst PWID. Although now more widely adopted, to date very few countries have achieved targets for opioid agonist therapy or met the recommended number of needles and syringes distributed per year. With less than 1% of total HIV spending allocated to programs for PWID globally, it is no surprise that PWID continue to be left behind in access to prevention and treatment programs. Far from its intended aim of protecting individuals and society from the harm of drug use, punitive drug laws and prohibition continue to result in diseases, deaths from drug overdoses, prison overcrowding, violence and a cycle of poverty. Drug use is often seen through a moral lens, with users stigmatized as criminals or morally deficient rather than individuals in need of help. This stigma makes it challenging to build public support for harm-reduction policies and programmes. Many fear that alternative approaches, such as legalization or decriminalization, could lead to unintended consequences, including increased drug use or addiction, despite evidence from countries like Portugal demonstrating otherwise. The “War on Drugs” relied on fear-based narratives and racialized rhetoric that continue to shape public opinion. This is compounded by global treaties, such as

the 1961 Single Convention on Narcotic Drugs, which tie nations to prohibitionist policies and make reform on an international scale more difficult. Despite these challenges, there is a growing recognition of the failure of prohibition and increasing momentum for reform. The success of alternative approaches, such as decriminalization and harm reduction, highlights the potential for treating drug use as a public health issue rather than a criminal one. However, overcoming the entrenched political, economic, and cultural barriers to change requires sustained effort, evidence-based policymaking, and a shift in public perception toward compassion and practicality over punishment. By leveraging evidence, building partnerships, and engaging in public discourse, the scientific community can challenge outdated drug policies and push for reforms grounded in science, equity, and compassion. Background: Antiretroviral therapy (ART) has transformed HIV-1 infection from a fatal disease into a manageable chronic condition. However, longitudinal studies reveal that the decay rate of the HIV-1 reservoir is so slow that ART alone cannot eliminate the reservoir within the lifetime of people living with HIV-1 (PLWH). This underscores the urgent need for safe and scalable strategies to achieve an HIV-1 cure. Most HIV-1 cure strategies fall into two main categories: (1) approaches aimed at eradicating or inactivating the reservoir and (2) approaches designed to induce immune-mediated control of the virus. Hematopoietic stem cell transplantation (HSCT) has demonstrated the potential to completely eradicate the HIV-1 reservoir, as seen in case reports of PLWH receiving HSCT for hematologic conditions. However, due to its inherent risks, HSCT is not a feasible cure strategy for otherwise healthy individuals. Consequently, most research has shifted toward strategies focused on immune-mediated control of HIV-1. Cytotoxic CD8+ T cells are strongly associated with spontaneous HIV-1 control, making the enhancement of CD8+ T cell immunity a promising avenue for clearing infected cells and achieving long-term viral suppression. Despite these prospects, therapeutic HIV-1 vaccines have so far failed to produce the desired results in clinical trials. Nevertheless, a range of other compounds - both those specifically designed for HIV-1 cure and repurposed drugs from fields such as oncology and hematology - have been investigated for their potential to impact HIV-1 persistence. While many of these interventions have not succeeded in significantly reducing the reservoir or inducing robust adaptive immune responses, recent trials have reported encouraging outcomes, with some individuals achieving partial or complete long-term control of HIV-1 after discontinuing ART. These findings raise the possibility that a functional cure for HIV-1 is achievable. In this talk, I will provide an overview of the most promising therapeutic strategies in the pursuit of an HIV-1 cure, including the use of broadly neutralizing antibodies. I will also discuss key populations that may have a higher likelihood of achieving a cure and address the critical barriers that remain in developing effective interventions. Additionally, I will review findings from in-depth studies of the biological mechanisms underlying sustained HIV-1 suppression in individuals who maintain control for years after stopping ART. Background: This "state of the pandemic plenary will review the current status of the global pandemic; interrogate recent available data on HIV incidence from placebo arms of RCT and PURPOSE trials; review data on mortality; elucidate the challenges of primary prevention in high HIV burden and lower HIV burden populations; explore the challenges of late diagnoses and advanced HIV disease; and suggest ways forward for an invigorated response using new prevention tools which could achieve epidemic control. The key themes and messages, supported by current evidence are that: • We did not meet the UNAIDS 2025 targets on HIV incidence or mortality and are not on track for 2030 • HIV incidence remains too high to achieve pandemic control • The social determinants of HIV incidence remain formidable barriers to prevention, treatment, and care • Both MSM and Trans communities globally, and women and girls in SSA, remain at high lifetime acquisition probability in multiple countries The Global HIV/AIDS Pandemic: Where Are We Now? Chris Beyrer Duke Global Health Institute, Durham, NC, USA HIV Cure: A Translational Research Perspective Ole Søgaard Aarhus University, Aarhus, Denmark

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Immune Responses During Viral Rebound Rachel Rutishauser University of California San Francisco, San Francisco, CA, USA

• 3 regions (E. Europe & Central Asia; Latin America, Middle East and North Africa) are in epidemic expansion in 2025. These regions have been underfunded, understudied, and uniquely challenged • Significant increases in primary prevention programs, access, coverage, and equity will be required to achieve epidemic control--treatment is necessary but insufficient Advances in primary prevention, including LA injectables, could markedly reduce HIV incidence but only if taken to scale for both high incidence density populations (MSM, SW, TGW, AWYG in high burden settings) AND lower incidence ones (general population reproductive age adults where incidence is above 1 and under 3/100 PY). Utilizing a Barcoded Virus Model to Identify the Source of Viral Rebound Brandon Keele Frederick National Laboratory for Cancer Research, Frederick, MD, USA Background: Current ART has the capacity to drastically suppress but not abolish previously infected cells which can persist for the life of the host. This persistent rebound competent virus is the primary barrier to HIV cure. This long-term stable virus resides in multiple subsets of CD4+ T cells, particularly CD4+ memory T cells, and possibly macrophages that are widely distributed throughout the body. To mediate post-ART viral rebound, viruses must be genetically intact and replication competent, but viral rebound is not a wholesale resumption of viral replication from all replication-competent genomes but rather reflects an initial oligofocal outgrowth of virus from a limited subset of the total infected cell population that subsequently spreads throughout the body. Despite the importance of understanding the clonal origins of post-ART viral rebound, virtually nothing is known about these early local dynamic events, due to challenges with sampling, variability in time to rebound, and limited genetic diversity between individual rebounding lineages with previous work studying viral rebound only at later viremic stages or in limited numbers of tissues. To overcome these challenges, we developed and validated a barcoded virus model (SIVmac239M) that contains a short, unique nucleotide insert allowing for genetic discrimination of over 10,000 viral lineages. We used viral barcode analysis from a comprehensive collection of tissue samples in a large cohort of SIV-infected, ART suppressed rhesus macaque during both on-ART and post-ART cessation, to identify the initial sites of rebound and patterns of subsequent viral spread. Our results indicate that it is possible to identify the earliest stages of local tissue-level post-ART rebound and that this early rebound preferentially occurs in gut and gut-draining lymph nodes. Pinpointing the anatomic sites of viral rebound can facilitate the identification of the mechanisms that specifically mediate these reactivation events in these specific tissues. Together, these observations may have potential therapeutic implications for interventions designed to prevent or control viral rebound. Background: Cellular and tissue sources of viral rebound primarily originate from long-lived reservoirs of HIV in individuals under antiretroviral therapy (ART). Key cellular reservoirs include CD4+ T cells , particularly memory subsets like central memory (Tcm), which harbor latent provirus. Tissue-specific sources include lymphoid tissues (lymph nodes, spleen, and gut-associated lymphoid tissue), where virus can persist despite ART. The central nervous system (CNS) acts as a sanctuary probably also due to limited drug penetration. Additionally, myeloid cells like macrophages and microglia may contribute to viral rebound. Gut tissue plays a significant role as it harbors high numbers of infected cells and provides a pro-inflammatory environment conducive to viral reactivation. In this presentation, we will explore methods used to characterize the persistent HIV reservoir across various cell subsets and tissues, highlighting their successes and limitations in identifying the viruses responsible for systemic rebound upon treatment interruption. Additionally, we will discuss how emerging technologies and multi-omics platforms can enhance our understanding of the viral reservoir and provide new insights into its dynamics and reactivation potential. Cellular and Tissue Sources of Viral Persistence and Rebound Linos Vandekerckhove HIV Cure Research Center, Ghent University, Ghent, Belgium

Background: The objectives of this talk are to: (1) define different patterns of HIV rebound (i.e., categories of post-ART control), (2) review examples of effective immune responses against HIV, focusing on immune mechanisms that have been implicated in post-ART control, and (3) discuss lessons learned about immune responses to rebound from recent ATI trials, including the UCSF-amfAR combination immunotherapy trial.

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Advanced HIV Disease in Children Pablo Rojo Hospital Universitario 12 de Octubre, Madrid, Spain

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Background: In 2025, late diagnosis of HIV in children continues to be a significant global concern, with many presenting with advanced HIV disease (AHD). This issue contributes to a considerable number of hospital admissions, particularly among infants, due to acute conditions such as pneumonia, sepsis, and diarrhea. These acute illnesses are frequently accompanied by important by sometimes subtler health issues, including malnutrition, anemia, and HIV related encephalopathy. As a result, there is an alarming mortality rate during hospital stays, coupled with notably high post-discharge mortality rates in the year that follows. The WHO STOP AIDS technical brief provides a vital framework of care for children with AHD, outlining clear intervention strategies; however, its implementation remains inadequate worldwide, especially in Sub-Saharan Africa. Furthermore, there is an urgent need for additional research to combat these unacceptably high mortality rates. Areas requiring investigation include the benefits of rapid PCR diagnostic confirmation in critically ill infants, enhanced strategies for both the prevention and treatment of malnutrition, clarification of the role of cytomegalovirus (CMV) in severe pneumonia and its management, and the formulation of effective prophylactic approaches for serious bacterial infections in the context of rising antibiotic resistance. Background: Children aged 0-15 years lag behind adults in achieving HIV treatment goals across HIV testing, initiation of antiretroviral therapy and viral suppression. While early diagnosis of pediatric HIV has scaled up significantly, children continue to slip through the cracks and remain undiagnosed and untreated. For children living with HIV, challenges in adherence to treatment is hampered by family and caregiving structures leaving children prone to poor viral suppression. Recent advances in treatment including newer dolutegravir based regimens and easy to use treatment formulations have improved adherence and viral suppression in children but gaps remain in achieving optimal viral suppression. This talk will focus on the state of the HIV care continuum for children aged 0-15 years, focusing on current trends, gaps and advances to improve the cascade of care in children. Sexual, Reproductive, and Pregnancy Health Among People With Perinatal HIV Caroline Foster Imperial College Healthcare NHS Trust, London, UK Background: Since 1990 an estimated 11 million children have been born with HIV and with the successful global role out of paediatric antiretroviral therapy (ART) increasing numbers of young people are transitioning through adolescence and entering adult care. In resourced settings with earlier access to ART the oldest survivors are now entering their 5th decade of life but with a legacy of years of unsuppressed viraemia and/or exposure to older more toxic ART agents. However survivor bias means they represent a unique cohort who survived childhood without access to ART, with slower disease progression and likely favourable host genetics and immune responses. In contrast many of those born in more recent decades started ART in early childhood and are more likely reflective of the emerging adolescent perinatal cohorts globally, important in identifying the consequences of lifelong HIV and ART exposure throughout postnatal, childhood and adolescent development in the ART era. This talk will follow the journey of a young person living with perinatal HIV through the unique challenges of adolescence, a period of life encompassing complex biological and psychosocial changes that include sexual maturation, development of sexual identity and the onset of sexual activity, through to pregnancy and parenthood. We will examine existing data on sexual and HIV Care Continuum in Children Irene Njuguna University of Washington, Seattle, WA, USA

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Abstract eBook

Invited Session

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HIV Acquisition and Prevention During Pregnancy and Postpartum John Kinuthia Kenyatta National Hospital, Nairobi, Kenya Background: This presentation will discuss HIV incidence during pregnancy and breastfeeding as well as factors (hormonal, immunological, behavioural, sexual and genital infections, and low male participation in antenatal care and HIV testing) that increase risk of HIV acquisition this period. In addition, we will look at the contribution of acute HIV infection to vertical HIV infection and underlying factors driving the increased risk of transmission. I will highlight existing HIV prevention interventions with focus on behavioural and biomedical interventions. Behavioural interventions discussed will include enhanced HIV counseling, use of lay community based workers to provide HIV prevention counselling and male partner referral for circumcision, sexually transmitted infections or HIV treatment implemented in several sub-Saharan African countries. The role of oral antiretroviral pre-exposure prophylaxis (PrEP) during pregnancy and breastfeeding, maternal and infant outcomes following PrEP use, importance of integrating PrEP delivery within maternal and child health clinics and whether a risk based approach is better compared to universal PrEP delivery model will be discussed. Barriers to oral PrEP uptake and continuation and perspectives of health providers on determinants that impact ability to deliver PrEP will be described. Strategies to promote PrEP use among pregnant and breastfeeding women including differentiated service delivery models will be discussed. The talk will also cover use of use of currently available long‐acting formulations that is carbotegravir, six-month injectable lenacapavir and dapivirine ring during pregnancy and breast feeding including efficacy, maternal and infant outcomes as well as effect of added choice of biomedical interventions on HIV prevention coverage. Potential challenges during implementation at scale and the role of all stakeholders including governments, donors, civil society, or manufacturers among others to ensure seamless and impactful rollout will be highlighted. There will be focus on requirements for provision of lenacapavir regarded as 2024 Breakthrough of the year by the Science Magazine. Lenacapavir represents a transformative opportunity to dramatically reduce the number of new HIV infections. Finally, we will deliberate on how to protect women through and NOT from research in order to reduce evidence gaps regarding safety and efficacy of new antiretroviral formulations during pregnancy and breastfeeding. Background: Although the development of effective vaccines has saved countless lives from infectious diseases, the basic workings of the human immune system are complex and have required the development of animal models, such as inbred mice, to define mechanisms of immunity. However, past results are not necessarily a reliable guide to the future, and a notable limitation of animal models has been their failure to accurately model some human diseases and their inability to predict human immune responses in many cases. In the past decade there has been an explosion of new approaches and technologies to explore the human immune system with unprecedented precision. Insights into the human immune response to vaccination, cancers, and viral infections such as COVID-19 have come from high-throughput “omics” technologies that measure the behavior of genes, mRNA, proteins, metabolites, cells, and epigenetic modifications, coupled with computational approaches. I will discuss how these “Systems Vaccinology” approaches are advancing our mechanistic understanding of the human system and its response to vaccines and infections and facilitating the development of vaccines against HIV and other infectious diseases. How HIV Capsid Breaches the Nuclear Envelope Through Karyopherin Mimicry David Jacques University of New South Wales, Sydney, Australia Background: As a lentivirus, HIV is capable of infecting non-dividing cells. For decades it has been understood that HIV must be able to deliver its genetic material across the nuclear envelope in order to establish infection. As the gatekeeper between the cytoplasm and the nucleus, the nuclear pore complex (NPC) represents an obvious entry point. During normal cellular function, the Systems Vaccinology Bali Pulendran Stanford University, Stanford, CA, USA

reproductive health for this unique cohort, born into a family living with HIV and the challenges of negotiating adolescence with a potentially sexually transmissible infection for the first and every subsequent sexual encounter and that sharing your status potentially discloses the status of other family members. We will focus on biomedical prevention strategies including sexual health education, vaccination, contraception and screening for sexually transmitted infections and for anogenital cancers. Increasing numbers of young people born with HIV are choosing to start families with pregnancy data emerging, including the early infant outcomes for a unique cohort of “3rd Generation” HIV exposed uninfected infants born to people who themselves have lived with HIV their entire lives. Finally we will identify data gaps in sexual, reproductive and pregnancy health for this cohort, highlighting future research questions and the importance of the meaningful inclusion of youth in setting the research agenda to support them in fulfilling their potential as adults, partners and parents. Immediate Challenges and Long-Term Goals of the HIV Response Jeffrey Imai-Eaton Harvard TH Chan School of Public Health, Boston, MA, USA Background: Over the past 25 years, the global HIV response has made remarkable progress at controlling HIV epidemics, including reducing new infections and ensuring healthy lives for people living with HIV. However, progress has not been equal across epidemic settings or populations affected by HIV, and overall remains off track to achieve targeted 90% reductions in new infections and AIDS-related deaths by 2030. This presentation will review immediate challenges impeding attaingment of these goals, including sustaining high coverage of effective programmes in high HIV burden settings, regions and epidemiologic settings with lagging in progress, and population groups with distinct unmet needs. Moreover, whilst there are opportunities to accelerate progress toward Ending AIDS as a Public Health Threat by 2030, even with a successful response the global community will continue to live with HIV for decades to come. We will discuss long-term goals in responding to HIV and needs and priorities to sustain effective HIV responses that safeguard and continue epidemiologic gains. Background: This presentation will delve into the complexities of sustaining the global HIV commitment amidst evolving health priorities and funding landscapes. This session will explore the opportunities and risks of integrating HIV care and prevention into broader health services. From innovative service delivery models to community-driven solutions, we will highlight how integration can enhance health system efficiency, reduce patient burden, and improve access to services. Participants will gain insights from global examples of successful integration strategies, and the challenges of maintaining focus on HIV in the face of competing priorities and declining donor funding. This presentation will discuss the dual imperatives of sustaining HIV-specific commitments and leveraging integration to achieve broader health goals. Discover how a people-centered, multisectoral approach can navigate risks such as weakened prevention efforts, service quality compromises, and fragmented systems. By addressing these challenges, we can seize the opportunities of integration to build resilient health systems and accelerate progress toward ending AIDS as a public health threat by 2030. Innovations in HIV Service Delivery: Building a Path Forward with Those Left Behind Izukanji Sikazwe Centre for Infectious Disease Research in Zambia, Lusaka, Zambia Background: Over the last 40 years, remarkable achievements have been recorded in the HIV response, with service delivery models that have increased access to HIV testing, expansion of the HIV prevention toolbox, availability of newer and less toxic antiretroviral therapy resulting in fewer people acquiring HIV in 2023 than at any point since the late 1980’s and almost 31 million people on treatment. Despite advances in science, individuals and communities continue to not access HIV prevention, care and treatment services. This session explores HIV service delivery innovations to bridge the gap and reach individuals and communities left behind. Integration and Stainability of the Global HIV Response Tsitsi Apollo Zimbabwe Ministry of Health and Child Care, Harare, Zimbabwe

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CROI 2025