CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

Oral Abstracts

detectable HIV DNA in CSF at ≥ 3 timepoints, based on a median of 4,400 cells assayed. There was no evidence for a decay in CSF HIV DNA over time ( Figure 1 ; p=0.8 from a censored-data model). The geometric mean of each participant’s CSF HIV DNA across time points correlated with the amount of HIV DNA in blood measured near the time of the first LP (r=0.45, p=0.09) but no correlations were evident with pre-ART plasma HIV RNA, pre-ART CD4 cell count, or duration of ART. Cell-free HIV RNA in CSF was only detectable in 2 participants, at 1 or 2 time points (3 of 77 assays performed, with levels 1-4 copies/mL). Cell-associated HIV RNA in CSF was detectable in 3 participants, each at a single time point. Conclusions: In a longitudinal study in which 4-5 serial LP were obtained over 2-4 years in people on ART for 6-19 years, HIV DNA was found to persist in CSF in most participants with no evidence of decay. These findings highlight the ongoing exposure of the CNS to infected cells during long-term ART, and the need to further understand the characteristics and pathobiological relevance of cells harboring HIV DNA in the CSF compartment. Single-Nuclei Multiome Analysis of CSF Cells Reveals Dendritic Cell Dysregulation Despite ART Michael J. Corley 1 , Chang Lu 2 , Paraskevas Filippidis 2 , Benjamin Orlinick 2 , Alina Pang 1 , Bibhuprasad Das 2 , Jennifer Chiarella 2 , Allison Nelson 2 , Sameet Mehta 2 , Serena Spudich 2 , Yuval Kluger 2 , Shelli Farhadian 2 1 Weill Cornell Medicine, New York, NY, USA, 2 Yale University, New Haven, CT, USA Background: Neurologic consequences of HIV linger even after viral suppression, suggesting a molecular “scar” that persists despite antiretroviral therapy (ART). However, whether innate immune cells in the cerebrospinal fluid (CSF) are altered during HIV and how they contribute to neuropathogenesis are poorly understood, owing in part to difficulties in isolating these rare populations of cells before the advent of single cell technologies. Methods: We enrolled 12 neurologically asymptomatic people with HIV (PWH) on suppressive ART and 11 demographically matched people without HIV (PWoH) for cross-sectional CSF single immune cell epigenome and transcriptome analyses. We utilized the 10X Genomics single nucleus multiome platform (ATAC-Seq + RNA-Seq), modified for low-cellular CSF, for 6 PWH and 5 PWoH (33,353 total nuclei). ATAC-seq data was used to identify open chromatin regions (peaks). We validated the single-nucleus transcriptomic data with additional data previously collected utilizing 10X 5’ single cell RNA-Seq from CSF of 7 PWH also on ART with features similar to the multiome participants and 6 PWoH (102,313 total cells). Results: CSF of both PWH and PWoH consisted primarily of T cells (median=89.5%; IQR=6.2%), and secondarily of myeloid cells (median=5.9%; IQR=6.5%), including a small percentage of dendritic cells (DCs) (median=2.4%;

IQR=1.7%). We identified 555 differentially accessible chromatin regions (DARs) across all cell types between PWH and PWoH. Despite comprising only a minority of CSF cells, DCs contained 32.8% of DARs, most of which were more open (more accessible) in PWH (130/182) (Fig. 1A). By annotating these DARs of DCs to their nearest genes, we identified 145 genes, including interferon-related genes IFI6 and GBP4 , both of which exhibit differential RNA expression between PWH and PWoH in DCs. In our validation dataset of 5’ single cell RNA-Seq CSF transcriptomes, we observed a DC transcriptomic signature in CSF of PWH compared to PWoH (Fig.1B). Pathway analysis identified downregulation of antigen processing and presentation, and cytokine (mainly IL-1 and IL-12) signaling in DCs in PWH. Lastly, we detected extremely rare HIV RNA and chromatin-accessible provirus DNA in CSF cells. Conclusions: Single-cell epigenome and transcriptome profiling of CSF suggests dysregulation of DCs in virally suppressed PWH. Further studies are needed to determine if these changes impair antigen presentation and antiviral responses, contributing to HIV persistence and neuropathogenesis. The figure, table, or graphic for this abstract has been removed. Plasma Phosphorylated Tau 217 and Cognitive Decline in Older Thai People With HIV Akarin Hiransuthikul 1 , Poosanu Thanapornsangsuth 2 , Watayuth Luechaipanit 2 , Thanaporn Haethaisong 2 , Sasiwimol Ubolyam 3 , Chuleeporn Wongvoranet 4 , Tanakorn Apornpong 4 , Win Min Han 5 , Hay Mar Su Lwin 4 , Napon Hiranburana 4 , Stephen Kerr 1 , Anchalee Avihingsanon 6 , for the HIV-NAT 006 and 207 Study Teams 1 Chulalongkorn University, Bangkok, Thailand, 2 King Chulalongkorn Memorial Hospital, Bangkok, Thailand, 3 Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 4 HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand, 5 Kirby Institute, Sydney, Australia, 6 HIV-NAT, Thai Red Cross AIDS and Infectious Disease Research Centre, Bangkok, Thailand Background: Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and accurate diagnosis is crucial, including for people with HIV (PWH). Blood-based biomarkers for AD offer a promising, low-cost, non invasive diagnostic alternative, but data are limited in PWH. Our study measured phosphorylated tau 217 (p-tau217)–the only blood-based biomarker currently recommended for diagnosing AD–and assessed its potential in predicting cognitive decline among virologically suppressed older Thai PWH. Methods: Blood samples were collected at baseline from virologically suppressed PWH aged 50 years and older, who completed the Thai-validated Montreal Cognitive Assessment (MoCA) at baseline (2015–2017) and a follow up visit (2021–2024). Cognitive impairment was defined as a MoCA score of less than 25. P-tau217 levels were measured and categorized by quartiles, with a binary comparison between quartile 4 (Q4) and quartile 1–3 (Q1–3). A multivariate linear mixed-effects model, adjusted for sex, education level, baseline MoCA score, HIV duration, nadir CD4 levels (<200 and ≥ 200 cells/ mm 3 ), and exposure to efavirenz, with an interaction term for baseline p-tau217 quartile and age, was used to estimate the effect of baseline p-tau217 levels on the changes in cognitive performance overtime. Results: A total of 255 PWH, with a median interval between MoCA of 5.9 years (IQR: 5.6–6.8), were included: 63.1% were male, median age was 54.3 years (IQR: 51.8–59.1), 76.1% had more than six years of education, median HIV

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CROI 2025