CROI 2024 Abstract eBook

Version 3 | Updated March 15, 2024

Abstract eBook

Contents

CONTENTS

Contents

ABSTRACT PROCESS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

INVITED SESSION PRESENTATION SUMMARIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

ORAL ABSTRACTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

POSTERS ABSTRACTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

DISCLOSURE OF FINANCIAL RELATIONSHIPS WITH INELIGIBLE COMPANIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414

AUTHORINDEX....................................................................................... 415

SEARCH TERM INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439

Version 3 | Last Updated on March 15, 2024 ©- Copyright 2024 CROI Foundation/IAS–USA. All rights reserved. ISBN #978-0-692-64664-9

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Abstract Process

ABSTRACT PROCESS Scientific Categories B asic Science A Virology of HIV, SARS-CoV-2, or Mpox Virus B Pathogenesis of HIV, SARS-CoV-2, or Mpox Virus: Human Studies and Animal Models C Host Immune Responses, Vaccines, and Immunotherapies: HIV, SARS-CoV-2, or Mpox Virus D HIV Reservoirs, Latency, and Curative Strategies Including Therapeutic Vaccines and Gene Therapy G Antiviral Therapy: Pre-Clinical Data, Randomized Trials, Efficacy, and Effectiveness Studies in HIV or SARS-CoV-2 or Mpox Virus 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, and Mpox Infections N Tuberculosis and Other Opportunistic Infections, Including the Impact of HIV or SARS-CoV-2 in Adults O Maternal and Fetal HIV, SARS-CoV-2, and Mpox Virus P Childhood and Adolescent HIV, SARS-CoV-2, or Mpox Virus 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 E Neuropathogenesis and Neurologic Complications of HIV and SARS-CoV-2 Infection and Neurologic Complications of HIV in Adults Clinical F Clinical Pharmacology in Adults 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 for HIV, and Impact of COVID-19 and Mpox on HIV-Related Programs

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 controlled trial in HIV infection [CROI Abstract 1261]. Abstracts From CROI 2024 Conference on Retroviruses and Opportunistic Infections. CROI 2024 Abstract eBook. 2024;583. 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 51 to 99 and 213 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. .

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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 ��������������������������������������������������������� 1682 General Abstracts Accepted ������������������������������������������������������������� 966 Late-Breaking Abstracts Submitted ������������������������������������������������ 220 Late-Breaking Abstracts Accepted ��������������������������������������������������� 101 Total Abstracts Accepted ������������������������������������������������������������ 1067 Ora Abstract Presentations ������������������������������������������������������� 111 Themes Discussion Presentations ��������������������������������������������� 54 Poster Presentations ����������������������������������������������������������������������956 Accepted Abstracts for Emerging Infections or Specific Populations SARS-CoV-2 ����������������������������������������������������������������������������������������� 193 Mpox ����������������������������������������������������������������������������������������������������� 33 Adolescents ����������������������������������������������������������������������������������������� 137 Men who have sex with men (MSM) ����������������������������������������������� 220 People Who Inject Drugs (PWID) ������������������������������������������������������� 84 Transgender Men or Women ������������������������������������������������������������� 84 Women or girls ����������������������������������������������������������������������������������� 259

Abstract Process

Please note: Figures, tables, or other graphics have been removed from the following abstracts due to noncompliance with the CROI Abstract Guidelines: 121, 133, 136, 175, 195, 209, 319, 336, 339, 345, 349, 359, 388, 424, 442, 490, 507, 510, 511, 530, 531, 534, 538, 549, 554, 557, 559, 561, 573, 594, 596, 602, 618, 629, 632, 658, 661, 662, 670, 694, 714, 721, 722, 726, 736, 741, 745, 761, 762, 764, 778, 781, 782, 794, 796, 803, 807, 812, 813, 824, 826, 843, 845, 860, 901, 923, 928, 947, 952, 968, 991, 1005, 1009, 1032, 1037, 1046, 1069, 1072, 1077, 1086, 1090, 1095, 1097, 1104, 1119, 1124, 1145, 1146, 1148, 1162, 1169, 1172, 1179, 1186, 1197, 1205, 1212, 1224, 1225, 1240, 1248

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Invited Session

INVITED SESSION PRESENTATION SUMMARIES

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Overview of the Scott M Hammer Workshop for New Investigators and Trainees Serena S. Spudich 1 , Katharine J. Bar 2 1 Yale University, New Haven, CT, USA, 2 University of Pennsylvania, Philadelphia, PA, 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 an annual 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, the program will begin with a presentation by Mr Adam Castillejo , an advocate and activist who will provide a community perspective on HIV cure. Dr Frank Kirchhoff will provide an overview of the molecular virology of HIV-1 and SARS-CoV-2 and describe key related presentations at CROI. Dr Elizabeth Connick will cover the immune responses against HIV and SARS-CoV-2. Dr Afam A Okoye will review advances in preclinical and clinical approaches for HIV remission or eradication. Dr LaRon E. Nelson will address advances in different strategies for preventing HIV transmission. Dr Jennifer Jao will provide an overview of key topics in maternal-child HIV and highlight relevant work presented at CROI. The workshop will end with a presentation by Dr Jeanne M Marrazzo , Director of the National Institute of Allergy and Infectious Diseases at the NIH, who will discuss opportunities in and provide insights on careers in research and discovery, reflecting on her personal career journey to date. By completing the workshop, attendees will have achieved a head start toward maximizing the knowledge gained and research ideas as they navigate CROI 2024. Background: Electron microscopy polyclonal epitope mapping (EMPEM) is a powerful technique for rapidly mapping the epitopes of serum antibodies and providing a visual readout of immune responses. EMPEM is performed using blood samples from immunized animal models, human volunteers, or convalescent patients of recent viral infection. Recently, our group has applied high resolution cryoEM methods to the same samples (cryoEMPEM) to visualize the amino acid interactions between antibodies and antigen. This approach can also be used to predict the sequences of the observed antibodies. By integrating NGS data of B cell repertoires with cryoEMPEM data, we are able to rapidly identify and provide unprecedented molecular resolution of epitope specific polyclonal antibody responses. EMPEM studies are complementary to traditional serological approaches, which altogether inform on the types of epitopes targeted, the diversity of epitopes targeted, and the consistency of epitopes targeted between study volunteers. When applied to HIV vaccine research, the molecular details revealed by this approach can confirm whether epitope specific, on-target antibodies are present in the sera and if they contain any structural and genetic features of known broadly neutralizing antibody precursors. A Spotlight on HIV: Visualizing Post-Entry Events by Correlative Light and Electron Microscopy Barbara Müller University Hospital Heidelberg, Heidelberg, Germany Background: The post-entry phase of HIV-1 replication - from cytosolic entry of the viral capsid encasing the genomic RNA to the integration of Cryoelectron Microscopy-Based Polyclonal Epitope Mapping (cryoEMPEM) Gabriel Ozorowski The Scripps Research Institute, La Jolla, CA, USA

the reverse transcribed viral cDNA into the host cell genome - has long represented an enigmatic part of the viral replication cycle. During this phase, subviral particles need to undergo a complex sequence of transitions in composition and structure, which is challenging to unravel using traditional bulk virological and biochemical approaches. Direct visualization of incoming viral structures in the cytosol by electron microscopy has been hampered by the difficulty to detect and identify rare, small objects with unknown morphology, which are embedded in a vast and complex cytosolic environment of similar electron density. Correlative Light and Electron Microscopy (CLEM) addresses this problem: rare, defined objects of interest are localized within a complex environment via fluorescence-based detection and subsequently analyzed with high spatial resolution using electron microscopic approaches. Today, continuous methodological advancements allow us to analyze the morphology of virus-derived complexes within their intracellular environment in unprecedented detail. Application of this approach to HIV-1 post-entry yielded new insights that, in conjunction with other results, identify the mature capsid as a key organizer of post-entry events. The presentation will introduce the CLEM approach and highlight insights into post-entry events in HIV-1 replication, from the visualization of cytoplasmic reverse transcribing complexes in infected cells approximately 20 years ago to recent high resolution in situ imaging of capsid-like structures in transit through the nuclear pore. Single-Virus Tracking: Capturing Fast, Three-Dimensional Viral Dynamics in Live Tissue Models Kevin Welsher Duke University, Durham, NC, USA Background: The epithelium is a nessential first barrier against viral infection. Understanding the interactions that enable pathogens to cross this complex barrier is critical to treating a wide range of diseases, including the recent SARS-CoV-2 pandemic. Single-virus tracking (SVT) is a potentially powerful tool to capture the molecular scale details of viral infection in live cells. SVT typically relies on fluorescence microscopy and can provide different insights from ensemble bulk experiments. However, the reliance on traditional fluorescence microscopy techniques has limited the application of SVT to mono-layer cell cultures with poor temporal resolution upon expansion to three-dimensional tissue models. In this presentation, we will detail current SVT methods and their advantages and limitations. We will then introduce a new active-feedback SVT method for overcoming the current limitations of SVT. This new method, called 3D Tracking and Imaging (3D-TrIm), uses fast, real-time measurement to "lock on" to a single virion and measure its dynamics at kHz or faster sampling rates across large three-dimensional spatial scales in live cells. We will demonstrate how 3D-TrIm captures transient viral contacts with the cell surface with millisecond temporal resolution, and how this new technique can translate SVT from simple monolayer cell culture models to more complex three-dimensional tissue models. Single-Cell Multi-Omics of HIV Cellular Reservoirs Iain C Clark University of California Berkeley, Berkeley, CA, USA Background: HIV persists indefinitely within tissue and blood cell reservoirs, necessitating life-long antiretroviral therapy (ART). Single-cell omics technologies represent a promising approach to understanding cells that harbor provirus, including the unique cell-intrinsic mechanisms that promote cell survival, proliferation, immune evasion, or HIV silencing. However, despite technological advances in single-cell analysis, there are several unique challenges to using these tools in HIV cure research. First, HIV-infected cells are rare in vivo, which necessitates the single-cell sequencing of hundreds of thousands of cells per sample, at great expense. Second, HIV accumulates in heterochromatin and may not express HIV RNA. Methods like scATAC-seq or scRNA-seq therefore only capture HIV+ cells with transcriptionally active

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Cirrhosis Management Mazen Noureddin Houston Research Institute, Houston, Texas

provirus and those in regions of open chromatin. Last, over 95% of HIV provirus in people on long-term ART are defective. Any method that seeks to understand cells with replication-competent virus must first identify the even rarer cell population that contains intact provirus. No technology has yet to address all of these challenges, but in recent years commercial scRNA-seq and scATAC seq platforms have allowed cure researchers to generate exciting datasets that begin to reveal how HIV persists during effective ART. These datasets, owing to the rarity of HIV+ cells, are large but contain only hundreds of HIV+ cells, presenting additional challenges during bioinformatic analysis and interpretation. Recently, we reported a custom droplet microfluidic technology, FIND-seq, for sorting HIV+ cells. Instead of barcoding every cell in a sample, FIND-seq allows for the isolation of HIV DNA+ cells and is compatible with the intact provirus detection assay (IPDA), which can differentiate many forms of defective provirus. In this talk, I will discuss single-cell analysis technologies, their application in HIV cure research, and the technical advances needed to sequence the replication-competent HIV reservoir. Background: Steatotic liver disease (SLD) is a rising cause of liver-related morbidity and mortality worldwide, including among persons with HIV (PWH). This presentation will review the new nomenclature for SLD, which is predominantly metabolic dysfunction-associated (MASLD) and can overlap with alcohol-related liver injury. We will also review the initial work-up of a patient with SLD and elevated liver enzymes, and we will discuss a stepwise approach to assessing for clinically significant fibrosis using non-invasive tests. Finally, we will review current management of PWH and SLD, including lifestyle modification, adjustment of potentially contributory medications, and pharmacologic interventions. Background: Worldwide, between 12 and 60 million people with chronic hepatitis B (HBV) are estimated to be coinfected with Hepatitis Delta (HDV). HDV infection is caused by a defective RNA virus which is only able to replicate in presence of HBV. Although international guidelines recommend testing of Hepatitis Delta in every person with chronic Hepatitis B-infection, HDV prevalence data and actual numbers are lacking as the testing coverage is poor. There is a wide variation of geographic HDV infection rates with highest prevalence rates in Eastern and central Europe, the Mediterranean basin as well as in West and Central Africa. Hepatitis Delta infection can be prevented through Hepatitis B vaccination, therefore worldwide coverage of Hepatitis B vaccination is indispensable. Shared transmission pathways for HIV, HBV and HDV result in an increased risk for HDV coinfection in persons with HIV (PWH). Recent European data reported HDV prevalence in PWH between 7% and 15%, with the highest rate in people who inject drugs. Interestingly, transmission risks and patterns may be subject to change, as data from Taiwan recently showed an increased HDV incidence in men who have sex with men (MSM). Moreover, increasing migration may also contribute to changes in HDV prevalence. HDV co-infection is known to cause the most aggressive course of liver disease in PWH leading to significantly more liver cirrhosis, hepatocellular carcinoma and eventually an increased rate of liver-related death. Therefore, wide screening coverage is mandatory to detect cases early. With the 2020 European approval of Bulevirtide, a novel entry-inhibitor blocking the HBV-HDV-specific receptor, a new HDV specific drug is now available for treatment of HDV infection as a daily subcutaneous injection. Treatment with Bulevirtide is recommended in persons with HIV/HBV-/HDV-co-infection with compensated liver disease according to EACS guidelines. Recent data have shown a good decline in HDV-RNA and normalization of liver enzymes in PWH which is in the range of HDV treatment responses in HBV/HDV coinfected subjects without HIV. The optimal duration of treatment however, as well as long-term data are still lacking. In conclusion HDV represents a frequently underdiagnosed critical health issue that needs more attention in order to increase HDV diagnosis rate and enable access to new HDV drugs, thereby improving the unfavorable outcome of HDV in HIV/ HBV-coinfection. Steatotic Liver Disease in Persons Living With HIV Jennifer Price University of California San Francisco, San Francisco, CA, USA Hepatitis Delta: What to Know, What to Do? Kathrin van Bremen University of Bonn, Bonn, Germany

Background: In our up coming cirrhosis management lecture, we'll cover the diagnosis and management of cirrhosis, with a focus on HIV patients. We'll discuss diagnostic methods, including medical history, physical exams, and advanced tests like liver function and imaging studies. For management, we'll explore lifestyle changes, pharmaceutical options for complications, and the challenges of concurrent HIV and cirrhosis treatment. Our goal is to provide a concise yet comprehensive overview to empower you with the knowledge needed to effectively diagnose and manage cirrhosis, particularly in the context of HIV. Overview of the Case-Based Workshop on Antiretroviral Therapy Rajesh T Gandhi Massachusetts General Hospital, Boston, MA, USA Background: In this session, Drs. Claudia Cortes and Rajesh Gandhi 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 drug-resistant HIV, treating people who are not able to take oral antiretroviral therapy (ART), managing ART during pregnancy, and ART considerations in the setting of HIV/TB coinfection. This fast-paced and exciting interactive session will illustrate current approaches to managing people with HIV and highlight high-priority areas for future research. Exploring Strategies to Measure and Understand Users' Preferences in HIV Prevention and Care José A Bauermeister University of Pennsylvania, Philadelphia, PA, USA Background: Advances in short- and long-acting pre-exposure prophylaxis (PrEP) and Antiretroviral Therapy (ART) have fueled the need to understand how individuals make trade-offs and competing decisions regarding their preferred PrEP and ART modalities. In this presentation, Dr. Bauermeister provides an overview of the state-of-the-science regarding how HIV researchers have conceptualized and measured users' preferences in HIV prevention and care studies. Dr. Bauermeister will describe key conceptual and methodological approaches to understanding users' preferences and choices, including a discussion on the value and trade-offs between Discrete Choice Experiments (DCEs), Conjoint Analysis (CJAs), and Stated Preference Methods. Using several case studies, Dr. Bauermeister will illustrate how these data may help characterize how users make decisions about HIV prevention and care regimens, inform market segmentation strategies to reach diverse types of potential users, and contribute to the development of more effective, user-centered clinical decision aids for PrEP and ART product selection and counseling. Insights into users' preferences hold significant implications for shaping future HIV prevention and care strategies, ensuring their alignment with user preferences, and ultimately advancing the field towards more tailored and effective interventions. Hybrid Effectiveness Implementation Studies: Unrecognized Challenges and Emerging Directions Elvin H Geng Washington University in St Louis, St Louis, MO, USA Background: Progress in the HIV response today depends on more than ever of use of rich toolbox of efficacious interventions (e.g., PrEP) with reach, equity, sustainability and quality in the real world. One source reason for existing gaps between identifying efficacious interventions and their use is the is traditional scientific sequence of first efficacy, then effectiveness and finally implementation trials. Hybrid trial designs - studies that seek to study both implementation as well as effectiveness simultaneously - offer important but incompletely realized opportunities to accelerate translational impact. The talk will cover current nomenclature and classification of hybrid trial types (e.g., "Type 1"), highlight current evolution in design and distill key insights that aim to have immediate implications for researchers conducting trials in HIV. In addition, however, I will turn attention to challenges inherent in hybrid designs that seek simultaneous investigation of implementation and clinical outcomes that are to date inadequately addressed. First, current literature in does not fully consider when and how different implementation strategies change observed subsequent clinical effects. I offer principles to help guide determination of relative importance of implementation vs. effectiveness outcomes and the

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of immunoprivileged tissues, 2) multiple ways to evade innate immunity, 3) antigenic diversity of infecting strains, 4) genetic variability and rapid T cell immune escape in infected persons, 5) Env conformational evasion of neutralizing antibodies, 6) Env glycan shield against neutralizing antibodies, 7) immunodominance of antigenic sites on Env with low vulnerability to neutralization, 8) paucity of Env targets on virions, 9) mucosal sites of infection, 10) infection of cells critical for induction of immunity, 11) infection of both lymphoid and antigen-presenting Fc-bearing cells, and 12) potential for infection by virus-infected cells as well as cell-free virions. Solving any of these difficult immunological problems creates a potential solution for other infectious and non-infectious diseases. In that respect, despite a small probability of success, working toward successful HIV vaccines has been and will continue to be one of the most productive scientific activities of our time. Reflections on Ending Pediatric HIV: Back to Basics, Confront the Unexpected, Challenge Assumptions Dorothy Mbori-Ngacha Formerly with United Nations Children’s Fund, New York Background: Over the past two decades remarkable progress has been made in our efforts to reduce vertical transmission of HIV, thanks to support for and investment in ending AIDS among children. Programmes for preventing the transmission of HIV during pregnancy, birth and breastfeeding have had significant impact and averted an estimated 3.4 million infections in children (aged 0–14 years) since 2000. Nevertheless, with 130 000 [90 000–210 000] new infections occurring among children globally in 2022, we are still off-track towards achieving our global target of eliminating vertical transmission as a public health threat by 2025. Each day in 2022, approximately 740 children became infected with HIV and approximately 274 children died from AIDS related causes, mostly because of inadequate access to HIV prevention, care, and treatment services. In this lecture I will highlight the programmatic developments – taking scientific innovations to scale in policies and programmes - that have underpinned efforts towards the elimination of mother-to-child transmission of HIV over the past decade. The presentation will draw lessons from our past successes and failures in our PMTCT programs and discuss potential approaches to use in addressing the remaining gaps. Key questions that the presentation will reflect on include: Who are we missing in our response? What do we need to do differently to achieve and sustain universal coverage of PMTCT programs? How can we accelerate progress to achieve our 2025 targets? Finally, potential areas for on-going research will be highlighted. Unveiling the Power of Uganda’s LGBTIQ Advocacy in Shaping HIV Response and Health Care Access Frank Mugisha Sexual Minorities Uganda (SMUG), Kampala, Uganda Background: Embark on an exploration of Uganda's ongoing battle against state-sponsored homophobia and transphobia, this presentation sheds light on the vital role of LGBTIQ advocacy in shaping the country's HIV response and healthcare access. In the face of eroding rule of law and political repression, discriminatory laws criminalizing consensual same-sex conduct have created an environment of fear and vulnerability. This has resulted in severe consequences, including family banishment, unemployment, and pervasive discrimination, further exacerbated by limited access to targeted healthcare for LGBTIQ Ugandans. Despite commendable achievements, such as thwarting the Sexual Offences Bill 2019 through tireless advocacy, the recent enactment of the Anti-Homosexuality Act 2023 presents a formidable challenge to healthcare access and health-seeking behavior. This presentation delves into the harsh realities confronted by the sexual and gender-diverse community, navigating a landscape deeply entrenched in religious propaganda and community driven initiatives for change. Join us on this journey as we explore the intricate interplay of policy, legislation, and the lived experiences of the LGBTIQ community, all while striving for progress in healthcare access amidst the alarming prevalence of HIV and STIs in Uganda. What's New in HIV Vaccines: Vaccine-Induced Immune Responses M Juliana McElrath Fred Hutchinson Cancer Center, Seattle, WA, USA Background: Development of an effective HIV vaccine remains an elusive goal. Yet the search has accelerated, driven by the imperative end HIV and new directions based on promising leads in preclinical and phase 1 clinical trials.

plausibility of their heterogenous effects across settings or populations. Second, hybrid designs have not fully addressed unanticipated "adverse" effects of implementation. The talk will therefore offer a typology of adverse effects from implementation strategies and ways researchers can capture such effects. Third, literature does not fully explore the role of implementation outcomes act as mediators of the effects of strategies on service delivery or clinical outcomes. I draw from modern epidemiological methods in mediation to highlight opportunities and pitfalls for analysis of hybrid trials, including potential utility of sequential randomization. Looking forward, I suggest that the next generation of hybrid designs can be improved by use of a causal or explanatory theory of how implementation strategies work and that use of causal diagrams can help to surface these mechanistic relationships. Throughout, I illustrate methodological principles with substantive issues importance to HIV field, such as long-acting injectable medications, differentiated service delivery models, HIV self-testing and other areas of contemporary importance. safety and efficacy data. While reviewing interim data, the DSMB may recommend stopping the study for efficacy, futility, harm, or toxicity. A recommendation to stop a study is based on a range of considerations, in this presentation we discuss these considerations. A study is stopped early for efficacy when there is strong evidence that an experimental arm of a study is statistically superior to a comparator arm. In this case, it is important to stop a study so participants and the community can receive the best care as early as possible. Deterrents to stopping a study early include: less data to examine secondary endpoints and subgroups, less safety data/long-term safety data, inconsistent results at end of study due to missing data at the interim analysis. A recommendation to stop a study early for futility can be based on effect size or logistics. Futility can be determined statistically when there is very low probability that there will be a significant result at the end of the study, based on current data and hypothesized future data. Logistical futility could occur if: enrollment is too slow to answer the scientific question while the question is relevant, there is a high dropout rate making the data difficult to interpret, or a lower-than-expected event rate leads to an underpowered study. Statistical errors are of concern when evaluating interim data for efficacy or futility and appropriate statistical procedures are needed. When monitoring for efficacy, it is important to not inflate the α level (the probability of incorrectly concluding the arms of a study are different). When monitoring for futility, it is important to not inflate the β level (the probability of incorrectly concluding the arms are not different). Statistical methods have been designed to appropriately control these errors when evaluating interim data. Stopping a study early is a difficult decision that must take many considerations into account. When recommending stopping a study, a DSMB must carefully balance benefits to study participants against the collective benefits that would be gained by accumulating additional study. Background: Structure-based vaccine antigen design has been a critical determinant of respiratory syncytial virus and SARS-CoV-2 vaccine success stories. Nucleic acid vaccines and vector-based vaccine delivery have been successfully developed for Ebola and COVID-19. The ability to identify B cell lineages with the capacity for broad neutralization and then target those B cells with novel antigens is being applied to new influenza vaccines. Nanoparticle display is being used for improved influenza, COVID-19, and RSV vaccine designs. Heterologous prime-boost vaccines are now approved for prevention of Ebola. Pseudotyped virus neutralization assays are routinely used to analyze immune responses to high virulence pathogens. Advances in flow cytometry and single cell sequencing have made rapid human monoclonal antibody discovery and repertoire analysis feasible. All of these concepts have common roots in efforts to make an HIV vaccine. Despite 40 years of effort and technological advances we still don't have an HIV vaccine. There are many reasons for this including: 1) rapid establishment of a reservoir of latently-infected cells and infection Stopping Clinical Trials Early: When and Why Sally Hunsberger National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Background: Monitoring accumulating data as studies are being performed is important. Data and Safety Monitoring Boards (DSMB) are an independent group of experts, established by the study sponsor, to review accumulating Modern Vaccinology: A Legacy of HIV Research Barney S Graham Morehouse School of Medicine, Atlanta, GA, USA

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into phase 1 clinical trials (NCT03547245, NCT05471076, NCT04224701). The emerging data from these trials, showing the effective priming of VRC01-class B cells in humans, provide proof of concept that the germline-targeting approach holds much promise. The challenges ahead include the further maturation of these VRC01-class B cells by 'shaping' and 'polishing' immunogens to generate bNAbs. Second, the strategy must be applied to other epitopes as an effective vaccine will likely require the induction of bNAbs against multiple epitopes. New developments in mRNA technology, adjuvant technology, and AI-based immunogen design will accelerate developing germline-targeting vaccination approaches that yield bNAbs. Novel Immunization Strategies to Move on Down the Road Darrell Irvine Massachusetts Institute of Technology, Cambridge, MA, USA Background: Progress is being made in the development of HIV Env immunogens with the potential to activate and expand B cell precursors capable of maturing to produce broadly neutralizing antibodies (bnAbs) that could protect against HIV infection. However, such precursors are generally very rare in the human B cell repertoire and must make challenging sets of mutations in their antigen receptors (via somatic hypermutation in germinal centers, GCs) in order to produce bnAbs. In addition, once expanded and matured, these B cells must be driven to differentiate into long-lived plasma cells that can produce high levels of protective circulating antibodies and provide long-lasting protection. These immunological challenges to the development of an HIV vaccine are being tackled by a variety of approaches to formulate engineering vaccine immunogens in a manner that can optimally stimulate the B cell response, amplify GC responses, and promote high titers of output antibody production. This talk will summarize recent advances in the design of nanoparticle immunogens, vaccine dosing schedules that augment the GC response, potent new adjuvants in development, and the use of new vaccine technologies such as mRNA to promote the humoral immune response. Epidemiology of Perinatally Acquired HIV Among Adolescents and Young Adults Mutsawashe Bwakura-Dangarembizi University of Zimbabwe, Harare, Zimbabwe Background: Adolescents (10–19 years) and youth (15–24 years) living with perinatally acquired HIV represent increasing proportions of people living with HIV. Improved access to antiretroviral therapy globally has resulted in children who acquire HIV around the time of birth or through breastfeeding surviving into adolescence. While many are thriving, a significant proportion face several challenges that can affect their long-term outcomes. In particular, poorly controlled HIV disease resulting from suboptimal early regimens and nonadherence, together with the toxicities of some ARV drugs, can predispose them to long-term sequelae including HIV-associated complications and other comorbidities. This talk will be focusing on the state of the epidemic, the global epidemiology and trends of perinatally acquired HIV among adolescents over the years in the different geographical locations. acquired HIV experience poorer HIV-related outcomes compared to younger children and adults with HIV, dying more often and experiencing greater challenges in terms of treatment adherence and staying in care. Historic Evolution of HIV and Mental Well-Being Among Adults Living With Perinatally Acquired HIV Ezer Kang Howard University, Washington, DC, USA Background: Adults living with perinatally acquired HIV (PHIV) in the United States (US) have experienced key historic epochs of an epidemic since the 1990s. They navigated four lifespan periods – childhood, adolescence, young adulthood, and adulthood - spanning over three decades of the HIV epidemic. This has indelibly shaped the contours of their development and mental health. Influenced by a "complex interplay of individual, social and structural stresses and vulnerabilities" (World Health Organization, 2022), mental health is not merely the absence of mental disorder – it is a state of mental well-being. This paper explores three dimensions of mental well-being – emotional, psychological, and social (Westerhof & Keyes, 2010) - among Black adults living with PHIV in the US, with a focus on their formation in concert with two historic markers – treatment innovation and illness stigma. Drawing from a qualitative study of 20 Black adults living with PHIV in New York City and a select review of the history of pediatric HIV in the US, three dialectic themes will be presented

Recent breakthroughs in understanding how broadly neutralizing antibodies interact with their target epitopes on the HIV envelope spike have led to new HIV envelope immunogen designs that may over time provide a path to eliciting these types of antibodies. Also, novel vaccine designs for inducing highly functional CD8+ T cells with antiviral activities. By leveraging new vaccine technologies and delivery systems, and tailored trial designs, we aim to speed up the pace of progress. Shall We Reach Human Papillomavirus Elimination in the Face of Inequity? Nelly R Mugo Kenya Medical Research Institute, Nairobi, Kenya Background: In the 1950s discovery and implementation of the 'Papsmear' was a game changer and saved millions of women from cervical cancer deaths. Seven decades later, 342,000 women die annually from cervical cancer, the most common human papilloma virus (HPV) infection associated cancer. The scientific world has made great strides in discovery and there is unequivocal scientific evidence of highly effective interventions to prevent, diagnose, and treat human papilloma virus associated diseases. The discovery of a highly effective prophylactic HPV vaccines, sensitive screening and effective treatment interventions led to the 2018 World Health Organization (WHO) call for Global elimination of cervical cancer, a disease almost entirely caused by high risk (hr) HPV infection. An effective vaccine has reduced HPV related morbidities across gender. Countries that have effectively implemented HPV vaccine and screening for pre-cancer lesions have met the threshold for elimination. Global variance in disease burden reflects inequity in access to health care services and challenges in implementation, and countries with high disease burden have low coverage to interventions. HPV self sampling, evidence and adoptation of single dose HPV vaccine are part of innovative strategies to increase uptake of effective interventions. The science world continuous to seek innovative interventions to close the gap to access to effective interventions, with efforts toward therapeutic HPV vaccine, medical therapy for pre-cancer lesions and implementation science. Is Global elimination for HPV infection feasible and does the world have what it takes to make it a Global reality? Neutralizing Antibody Protection: Where Do We Go From Here? Yunda Huang Fred Hutchinson Cancer Center, Seattle, WA, USA Background: The Antibody Mediated Prevention (AMP) trials did not demonstrate HIV prevention efficacy (PE) of the CD4-binding-site-targetting broadly neutralizing antibody (bnAb), VRC01 (10mg/kg or 30mg/kg IV vs. placebo). However, 75% PE was observed against viruses sensitive to VRC01 with an IC 80 200 at the estimated time of exposure to a given exposing virus was associated with high PE, validating in humans consistent patterns observed in non-human primate (NHP) challenge studies of different single bnAbs. This knowledge can be applied to predict PE of combinations of long-acting LS modified bnAbs targeting non-overlapping HIV epitopes. As with combination anti-retroviral-therapy for HIV treatment, combination bnAbs may overcome neutralization resistance and provide more potent coverage for HIV prevention. Background: It is generally believed that an HIV-1 vaccine should induce broadly neutralizing antibodies (bNAbs), but no vaccine candidate so far has been able to do so effectively. A critical step in the generation of HIV-1 bNAbs is the activation of specific naïve B cells expressing germline antibody precursors that have the potential to evolve into bNAbs. However, envelope glycoprotein (Env) vaccine candidates are generally unable to do so unless specifically modified. Initial germline-targeting vaccine design approaches have focused on VRC01-class B cells named after the first known bNAb of this class. VRC01-class B cells are attractive targets for germline targeting the following reasons: 1) the AMP trial showed that when present at high titer, VRC01 can protect humans from HIV-1 acquisition; 2) VRC01-class bNAbs have been isolated from multiple HIV-1 infected individuals indicating that the human immune system can reproducibly generate such bNAbs; 3) they target the conserved CD4 binding site on HIV-1 Env, limiting the opportunities for viral escape and 4) they have a very specific and distinct genetic signature (a heavy chain derived from VH1-2 combined with a light chain with an unusually short 5 amino acid CDRL3). Three VRC01-class germline-targeting 'priming' vaccine candidates have moved Germline Targeting Strategies to Get On the Road Again Rogier W Sanders Academic Medical Center, Amsterdam, Netherlands

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communities, healthcare providers, and pregnant women about syphilis risks, the importance of antenatal care, and available preventive measures is crucial to increase awareness and enable early intervention in CS cases. Syphilis, despite being an ancient infection, presents ongoing challenges that require strategic approaches to enhance the healthcare network's capacity and improve the quality of care provided to pregnant women.

and aligned with emotional well-being (Terminal Illness vs. Chronic Condition), psychological well-being (Innocence vs Culpability), and social well-being (Visibility vs. Invisibility). These findings suggest that historic narratives of the HIV epidemic, and its many iterations, have enduring effects on individual narratives of mental well-being among a welcomed generation of adults living with PHIV. Cardiometabolic Risks and Complications: Adolescents and Young Adults With Perinatally Acquired HIV Sahera Dirajlal-Fargo Ann and Robert Lurie Children's Hospital, Chicago, IL, USA Background: Antiretroviral therapy (ART) scale-up has dramatically reduced rates of pediatric HIV mortality and morbidity. Children living with perinatally acquired HIV (PHIV) are living through adolescence and well into adulthood, such that adolescents now represent the largest growing population living with HIV. This presentation aims to discuss the literature describing the prevalence of cardiometabolic complications and the research gaps that remain, as well as opportunities to optimize research and care. There are continued challenges in determining the risk of cardiometabolic co-morbidities in adolescents and young adults with PHIV, and their risk factors differ compared to adults with horizontally acquired HIV. Data suggest evidence for subclinical cardiometabolic complications in PHIV in the setting of newer ART and include: 1) Cardiovascular: evidence of functional cardiac abnormalities, subclinical vascular disease and endothelial dysfunction; 2) Metabolic: evidence of alterations in adipose tissues, dyslipidemia and insulin resistance. In addition, previous exposure to thymidine analogues continue to cause increase risk of metabolic complications in this population. Novel techniques available techniques in imaging and omics may help identify early cardiometabolic abnormalities in this population as well as mechanistic pathways. Further studies are needed to understand the long term risk and management strategies in adolescents with PHIV to prevent complications to avoid diabetes and cardiovascular disease. Background: Congenital syphilis (CS) is transmitted from an infected mother to her unborn child during pregnancy, leading to severe health complications such as stillbirth, miscarriage, infant death, and maternal and infant morbidity. These adverse outcomes can be prevented through timely screening and treatment during antenatal care. The increasing prevalence of CS is associated with several challenges, requiring a comprehensive approach involving improved healthcare infrastructure, enhanced access to antenatal care, strong testing and screening programs, and extensive education initiatives to mitigate the impact on maternal and child health. Addressing the underdiagnosis of syphilis in pregnancy, especially in regions with limited healthcare access, is essential to avoid missed opportunities for screening and early detection. While reliable and accessible syphilis testing during pregnancy, including treponemal and non-treponemal tests, is essential for early detection, challenges may arise due to limited testing facilities, cultural stigma, and the complexity of implementing comprehensive screening programs. Ensuring that infected pregnant women receive timely and appropriate penicillin treatment is another critical measure to prevent CS, as penicillin is the only effective treatment during pregnancy. However, challenges such as limited healthcare access, potential allergic reactions, and penicillin shortages in some countries must be addressed. The stigma surrounding sexually transmitted infections and societal attitudes can discourage pregnant women from seeking testing, treatment, and follow-up care. Therefore, addressing these sociocultural factors is essential to create an environment where pregnant women feel comfortable accessing healthcare services. Despite specific recommendations from the World Health Organization aligned with sustainable development goals, CS remains a public health concern in many countries, with higher rates in developing countries and emerging cases in developed nations. Educating Why Can't We Do Better at Diagnosing Syphilis? Ina Park University of California San Francisco, San Francisco, CA, USA Background: This session will utilize challenging case studies to review methods for syphilis diagnosis, including direct detection, serology (non treponemal and treponemal tests), molecular diagnostics and point of care testing. The Burgeoning Epidemic of Congenital Syphilis Angelica Espinosa Miranda Ministry of Health of Brazil, Brasilia, Brazil

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Syphilis: Management Conundrums Khalil G Ghanem The Johns Hopkins University, Baltimore, MD, USA

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Background: As the rates of syphilis continue to increase, clinicians are caring for patients with complex clinical presentations, and they are facing challenging management dilemmas. In this session, we will answer the following questions: How do we approach rapid plasma reagin (RPR) titers that fail to decline appropriately following therapy? RPR titers that increase following treatment? What is the optimal management of patients with neurosyphilis, ocular, and otic syphilis? Are additional doses of benzathine penicillin G necessary in patients with these complications? How could DOXY-PEP impact the management of syphilis? Approaches that provide consistency in the care of patients with complex presentations of syphilis are feasible despite a paucity of data. HIV Assembly, Maturation Inhibitors, and Drug Resistance Eric O Freed National Cancer Institute, Frederick, MD, USA Background: HIV-1 particle assembly is driven by the viral Gag polyprotein precursor, which initiates assembly by forming an immature Gag lattice at the inner leaflet of the infected cell plasma membrane. Following completion of immature particle assembly and virus budding, the viral protease (PR) cleaves the Gag precursor at a number of sites to generate the mature Gag proteins matrix (MA), capsid (CA), nucleocapsid (NC), p6, and two small spacer peptides SP1 and SP1. PR-mediated Gag cleavage triggers a morphological transformation of the nascently released virion (known as maturation) during which the newly liberated CA protein assembles to form the viral capsid, into which are packaged the viral RNA genome and the viral enzymes reverse transcriptase (RT) and integrase (IN). Our work and that of others has demonstrated that the finely tuned stability of the immature Gag lattice is essential for particle assembly and subsequent maturation, and proper capsid stability is essential for early post-entry events. The stability of immature and mature Gag lattices is modulated by the cellular polyanion inositol hexakisphosphate (IP6). From a translational perspective, two classes of HIV-1 inhibitors - maturation inhibitors and capsid inhibitors (including the recently FDA-approved drug lenacapavir) - act by tipping the stability/ instability balance of the immature Gag lattice and the mature capsid, respectively. Thus, elucidating the determinants of Gag complex stability is crucial for both achieving a basic understanding of HIV-1 replication and also for moving forward drug discovery efforts that target assembly, maturation, or capsid-mediated post-entry events, including nuclear import. In a separate line of investigation, our recent work has shown that the lipid composition of the HIV-1 virion plays a key role in HIV-1 maturation, as disrupting the cellular lipid biosynthesis enzyme neutral sphingomyelinase 2 (nSMase2) blocks Gag processing, particle maturation, and virus replication. In all of the above described studies, drug resistance selections and forced evolution experiments have provided key mechanistic insights. Accelerating Tuberculosis Elimination: Short-Course Prevention and Treatment Vidya Mave Center for Infectious Diseases in India, Johns Hopkins India, Pune, India Background: Tuberculosis (TB) is among the leading cause of morbidity and mortality from an infectious disease, among patients with and without HIV, worldwide. Despite cost-free 6- months anti-TB therapy (ATT), the cure rates for TB have been suboptimal due to inadequate exposure/ adherence to ATT, causing a higher risk of failure, relapse, or acquired drug resistance, particularly in the setting of HIV. Recent research developments demonstrated that highly potent ATT regimens can allow shortening of TB treatment for both drug-sensitive and drug resistant TB in adult, adolescent and paediatric populations. In addition, shortened TB preventive therapy containing highly potent rifamycins and isoniazid is as good as the traditional 6-9 months of isoniazid prophylaxis among at-risk populations. Furthermore, emerging evidence shows that shortened course TB treatment and prevention regimens

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