CROI 2025 Abstract eBook

Abstract eBook

Invited Session

20

Immune Responses During Viral Rebound Rachel Rutishauser University of California San Francisco, San Francisco, CA, USA

• 3 regions (E. Europe & Central Asia; Latin America, Middle East and North Africa) are in epidemic expansion in 2025. These regions have been underfunded, understudied, and uniquely challenged • Significant increases in primary prevention programs, access, coverage, and equity will be required to achieve epidemic control--treatment is necessary but insufficient Advances in primary prevention, including LA injectables, could markedly reduce HIV incidence but only if taken to scale for both high incidence density populations (MSM, SW, TGW, AWYG in high burden settings) AND lower incidence ones (general population reproductive age adults where incidence is above 1 and under 3/100 PY). Utilizing a Barcoded Virus Model to Identify the Source of Viral Rebound Brandon Keele Frederick National Laboratory for Cancer Research, Frederick, MD, USA Background: Current ART has the capacity to drastically suppress but not abolish previously infected cells which can persist for the life of the host. This persistent rebound competent virus is the primary barrier to HIV cure. This long-term stable virus resides in multiple subsets of CD4+ T cells, particularly CD4+ memory T cells, and possibly macrophages that are widely distributed throughout the body. To mediate post-ART viral rebound, viruses must be genetically intact and replication competent, but viral rebound is not a wholesale resumption of viral replication from all replication-competent genomes but rather reflects an initial oligofocal outgrowth of virus from a limited subset of the total infected cell population that subsequently spreads throughout the body. Despite the importance of understanding the clonal origins of post-ART viral rebound, virtually nothing is known about these early local dynamic events, due to challenges with sampling, variability in time to rebound, and limited genetic diversity between individual rebounding lineages with previous work studying viral rebound only at later viremic stages or in limited numbers of tissues. To overcome these challenges, we developed and validated a barcoded virus model (SIVmac239M) that contains a short, unique nucleotide insert allowing for genetic discrimination of over 10,000 viral lineages. We used viral barcode analysis from a comprehensive collection of tissue samples in a large cohort of SIV-infected, ART suppressed rhesus macaque during both on-ART and post-ART cessation, to identify the initial sites of rebound and patterns of subsequent viral spread. Our results indicate that it is possible to identify the earliest stages of local tissue-level post-ART rebound and that this early rebound preferentially occurs in gut and gut-draining lymph nodes. Pinpointing the anatomic sites of viral rebound can facilitate the identification of the mechanisms that specifically mediate these reactivation events in these specific tissues. Together, these observations may have potential therapeutic implications for interventions designed to prevent or control viral rebound. Background: Cellular and tissue sources of viral rebound primarily originate from long-lived reservoirs of HIV in individuals under antiretroviral therapy (ART). Key cellular reservoirs include CD4+ T cells , particularly memory subsets like central memory (Tcm), which harbor latent provirus. Tissue-specific sources include lymphoid tissues (lymph nodes, spleen, and gut-associated lymphoid tissue), where virus can persist despite ART. The central nervous system (CNS) acts as a sanctuary probably also due to limited drug penetration. Additionally, myeloid cells like macrophages and microglia may contribute to viral rebound. Gut tissue plays a significant role as it harbors high numbers of infected cells and provides a pro-inflammatory environment conducive to viral reactivation. In this presentation, we will explore methods used to characterize the persistent HIV reservoir across various cell subsets and tissues, highlighting their successes and limitations in identifying the viruses responsible for systemic rebound upon treatment interruption. Additionally, we will discuss how emerging technologies and multi-omics platforms can enhance our understanding of the viral reservoir and provide new insights into its dynamics and reactivation potential. Cellular and Tissue Sources of Viral Persistence and Rebound Linos Vandekerckhove HIV Cure Research Center, Ghent University, Ghent, Belgium

Background: The objectives of this talk are to: (1) define different patterns of HIV rebound (i.e., categories of post-ART control), (2) review examples of effective immune responses against HIV, focusing on immune mechanisms that have been implicated in post-ART control, and (3) discuss lessons learned about immune responses to rebound from recent ATI trials, including the UCSF-amfAR combination immunotherapy trial.

21

Advanced HIV Disease in Children Pablo Rojo Hospital Universitario 12 de Octubre, Madrid, Spain

18

Invited Session

Background: In 2025, late diagnosis of HIV in children continues to be a significant global concern, with many presenting with advanced HIV disease (AHD). This issue contributes to a considerable number of hospital admissions, particularly among infants, due to acute conditions such as pneumonia, sepsis, and diarrhea. These acute illnesses are frequently accompanied by important by sometimes subtler health issues, including malnutrition, anemia, and HIV related encephalopathy. As a result, there is an alarming mortality rate during hospital stays, coupled with notably high post-discharge mortality rates in the year that follows. The WHO STOP AIDS technical brief provides a vital framework of care for children with AHD, outlining clear intervention strategies; however, its implementation remains inadequate worldwide, especially in Sub-Saharan Africa. Furthermore, there is an urgent need for additional research to combat these unacceptably high mortality rates. Areas requiring investigation include the benefits of rapid PCR diagnostic confirmation in critically ill infants, enhanced strategies for both the prevention and treatment of malnutrition, clarification of the role of cytomegalovirus (CMV) in severe pneumonia and its management, and the formulation of effective prophylactic approaches for serious bacterial infections in the context of rising antibiotic resistance. Background: Children aged 0-15 years lag behind adults in achieving HIV treatment goals across HIV testing, initiation of antiretroviral therapy and viral suppression. While early diagnosis of pediatric HIV has scaled up significantly, children continue to slip through the cracks and remain undiagnosed and untreated. For children living with HIV, challenges in adherence to treatment is hampered by family and caregiving structures leaving children prone to poor viral suppression. Recent advances in treatment including newer dolutegravir based regimens and easy to use treatment formulations have improved adherence and viral suppression in children but gaps remain in achieving optimal viral suppression. This talk will focus on the state of the HIV care continuum for children aged 0-15 years, focusing on current trends, gaps and advances to improve the cascade of care in children. Sexual, Reproductive, and Pregnancy Health Among People With Perinatal HIV Caroline Foster Imperial College Healthcare NHS Trust, London, UK Background: Since 1990 an estimated 11 million children have been born with HIV and with the successful global role out of paediatric antiretroviral therapy (ART) increasing numbers of young people are transitioning through adolescence and entering adult care. In resourced settings with earlier access to ART the oldest survivors are now entering their 5th decade of life but with a legacy of years of unsuppressed viraemia and/or exposure to older more toxic ART agents. However survivor bias means they represent a unique cohort who survived childhood without access to ART, with slower disease progression and likely favourable host genetics and immune responses. In contrast many of those born in more recent decades started ART in early childhood and are more likely reflective of the emerging adolescent perinatal cohorts globally, important in identifying the consequences of lifelong HIV and ART exposure throughout postnatal, childhood and adolescent development in the ART era. This talk will follow the journey of a young person living with perinatal HIV through the unique challenges of adolescence, a period of life encompassing complex biological and psychosocial changes that include sexual maturation, development of sexual identity and the onset of sexual activity, through to pregnancy and parenthood. We will examine existing data on sexual and HIV Care Continuum in Children Irene Njuguna University of Washington, Seattle, WA, USA

22

19

23

9

CROI 2025