CROI 2025 Abstract eBook

Abstract eBook

Invited Session

36

Long-Acting Treatments for Tuberculosis Eric Nuermberger The Johns Hopkins University, Baltimore, MD, USA

In the United States and high-income countries, the high cost of cabotegravir the intricate medication acquisition pathways for health centres delay national implementation. Healthcare organizations face intense staffing requirements for medication acquisition, insurance paperwork, process documentation, billing, injection administration, appointment scheduling, and client follow-up. Low- and middle-income countries (LMICs) face limited availability and access to cabotegravir. The production of generic medication is a lengthy process, with the first generic dose expected by 2027 for LMICs. PEPFAR's potential aggressive rollout in Africa, which involved purchasing and distributing the medication, faces setbacks. Global Fund, PEPFAR, and the Bill and Melinda Gates Foundation (BMGF) announced efforts to ensure two million people have equitable access to affordable Lenacapavir for three years. Recent termination of several PEPFAR grants further complicates these efforts. Overcoming the implementation challenges of cabotegravir, the first long-acting agent to market, will offer valuable lessons for future agents like Lenacapavir, administered every six months.The potential for LA PrEP to revolutionize HIV prevention is immense, but scaling it effectively requires addressing the aforementioned barriers and ensuring equitable access across different regions. Background: Long Covid is a disabling post-viral disease state that impacts over 400 million people worldwide, with no effective treatment currently available. Despite incomplete mechanistic understanding, lack of clinically actionable biomarkers, and insufficient policymaker recognition, significant progress has been made in recent years, revealing a clear histological and pathophysiological basis for the condition. SARS-CoV-2 infection prompts a complex immune response involving both innate and adaptive responses and immunothrombosis mechanisms. The virus infects multiple cell types and tissues, primarily those expressing ACE-2, including enterocytes, cardiomyocytes, and vasculature. Tissues with lower ACE-2 expression, like the brain, might be affected indirectly via immune-mediated and microthrombotic events. ACE-2 expression varies with disease severity and immune activation, including macrophage infiltration and microthrombi. Following acute infection, viral antigens may persist in tissues for years, continuously modulating the immune system, although they are inconsistently found in plasma. Acute systemic tissue injury releases host cell antigens which trigger autoimmunity. Enterocyte infection, inflammation, and antibiotic therapy during early Covid-19 cause gut microbial dysbiosis, which parallels the disease course. Microvascular damage and thrombosis result from endothelial damage, platelet infection, and activation of complement and coagulation cascades, leading to tissular hypoxemia, apoptosis, necrosis, and organ dysfunction. Mitochondrial respiratory chain changes and altered glucose and tryptophan metabolism worsen tissue damage, contributing to exercise intolerance and muscle necrosis post-exercise. All these and additional factors, like cranial nerve, suprarenal, or pancreatic dysfunction, contribute to long Covid's diverse clinical presentation. Host tissue susceptibility, predisposition, and functional reserve, but also stochastic phenomena, influence individual clinical presentations. Long Covid affects individuals with over 150 potential symptoms impacting various organs and systems, often with a remitting-relapsing course. However, 10 to 15 core symptoms help identify symptom clusters, aiding targeted mechanistic studies and clinical trials. Despite its complexity, Long Covid is being understood at a pace never seen before. The recent NIH Recover-TLC initiative represents a unique opportunity to advance towards finding a cure for this disease. Long COVID: Causes, Consequences, and the Way Forward Roger Paredes IrsiCaixa, Badalona, Spain Background: People with HIV (PWH) are facing multiple challenges in the battle against weight gain, including the growing, worldwide obesity epidemic and its drivers, normal aging and HIV- and antiretroviral therapy (ART)- associated contributors. The worldwide obesity epidemic is beyond the scope of this talk but must be considered when assessing individual patient risk and treatment options. HIV itself appears to promote fat gain and lean mass loss greater than expected for age, creating additional challenges. Finally, while ART initiation is universally associated with generalized weight gain, some PWH experience excessive (>10%) weight gain following initiation of or switch to Weight Gain in People With HIV Jordan E. Lake University of Texas Health Science Center at Houston, Houston, TX, USA

Background: Long-acting injectable formulations are revolutionizing HIV treatment and prevention and have similar potential to improve the treatment and prevention of tuberculosis, including simpler, shorter regimens and expanded treatment options. This presentation will describe how long-acting injectable formulations could address important obstacles to ending the world’s oldest pandemic, review recent progress in the development of long-acting tuberculosis drugs, and discuss future research needs and priorities. Background: This talk will highlight the burden and spectrum of post tuberculosis disease, focusing on the complexities of clinical presentation and pitfalls in assessment. We will give an overview of pathogenesis, and an update of recent work in post-tuberculosis lung disease (PTLD). We will highlight important knowledge gaps in the field, and will discuss ongoing work and needed efforts for both the future prevention and management of PTLD. Game Changed: Navigating the Era of Long-Acting Therapies for HIV Prevention Jonathan Li Brigham and Women's Hospital, Boston, MA, USA Background: We are at the dawn of a new era of long-acting antiretroviral (ARV) agents that promises to revolutionize the prevention of HIV infection. The HPTN083 and 084 studies first demonstrated the promise of cabotegravir for HIV pre-exposure prophylaxis (PrEP), but its use needs to be balanced with frequent injections, risks of drug resistance and challenges in diagnosing breakthrough infections. Lenacapavir represents the next leap forward for HIV PrEP with every 6 month dosing and impressive efficacy in recently completed clinical trials that led to its designation as Science’s 2024 Breakthrough of the Year. We will review the promise and challenges of these and other long-acting ARV options, including dapivirine ring and other novel approaches in development. Background: Is testing the key to unlocking PrEP scale-up? The use of antiretroviral drugs (ARVs) to prevent new HIV infections has been well established for decades, particularly in the context of pre-exposure prophylaxis (PrEP). Yet, only an estimated 2.5 million people are currently using PrEP—far fewer than the 10 million needed to meet global HIV prevention goals by the end of 2025. A key barrier to PrEP scale-up is the challenge of HIV testing, which often requires frequent facility visits and relies on complex and costly testing technologies and algorithms. This session will present the latest evidence and best practices to ensure safe, accurate, and effective HIV testing, including self-testing, as part of PrEP delivery across various agents and service delivery models. It will also address emerging data on Long-acting Early Viral Inhibition (LEVI) with long-acting PrEP agents and propose a public health approach to testing that can support the implementation of these evolving PrEP tools. Long-Acting Preexposure Prophylaxis: Why Can’t We Get to Scale? Cissy Kityo Joint Clinical Research Centre, Kampala, Uganda Background: In the past 12 years, 6.2 million individuals globally have been prescribed PrEP since its initial approval by the US FDA. The majority of these prescriptions, 1.4 million, have been issued in the past two years. However, oral PrEP's effectiveness is contingent on high adherence, posing challenges for certain high-risk groups. Research indicates that long-acting injectable PrEP (cabotegravir and Lenacapavir) surpasses oral PrEP in efficacy. LA PrEP offers a broader range of effective and acceptable prevention choices, overcoming oral tablet use challenges and enhancing prevention uptake. Despite LA Cabotegravir (CAB) being approved by the US FDA in 2021 and by the WHO in 2022, its rollout has been sluggish. Only approximately 11,000 prescriptions for CAB LA have been issued in the US since approval, compared to an estimated 382,000 annual PrEP users. Globally, especially in the global South, CAB-LA has seen limited uptake, primarily through implementation science projects in Africa and Asia. Post-Tuberculosis Disease: Opening Pandora's Box Brian Allwood Stellenbosch University, Cape Town, South Africa Complexities of HIV Diagnosis: What Lies Beneath Cheryl C. Johnson World Health Organization, Geneva, Switzerland

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Invited Session

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CROI 2025