CROI 2024 Abstract eBook

Abstract eBook

Invited Session

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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CROI 2024