CROI 2024 Abstract eBook

Abstract eBook

Invited Session

8

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

Invited Session

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CROI 2024