CROI 2025 Abstract eBook

Abstract eBook

Invited Session

7

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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Invited Session

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CROI 2025