CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

this study, we investigated this relationship to better understand how antigen exposure duration influences the evolution of HIV-specific T cell receptors (TCRs). Methods: This study included twelve female participants from the FRESH (Females Rising Through Education, Support, and Health) cohort, all of whom were identified in Fiebig stage I/II and had the protective HLA-B58:01 genotype and well-defined periods of detectable viremia before ART-mediated suppression. We defined the autologous HLA-B*58:01 -epitope sequences and then used barcoded tetramer labeling to FACS-sort HIV-reactive T cells. Targeted V(D)J and CITE-Seq enrichment was performed using 10X Genomics, with data processed through Cell Ranger and Seurat. Statistical analyses, including dot plots, non-parametric correlations (Spearman), and Mann-Whitney U tests, were conducted using GraphPad Prism 8.0. All subjects were evaluated following complete viral suppression to define the T cell repertoire. Results: We observed variability in T cell responses to HIV epitopes restricted by the HLA-B*58:01 allele during the acute phase of HIV-1 infection, with minimal detectable ex-vivo responses in individuals treated earliest during the acute phase. In each case, the immunodominant autologous epitope generated in participants was capable of stabilizing HLA-B*58:01 surface expression. Following complete suppression of viremia with ART, analysis of peripheral blood mononuclear cells revealed a significant enrichment of high-avidity HIV-specific TCRs in individuals with limited antigen exposure compared to those with prolonged exposure (p<0.0001). This enrichment was consistent across three immunodominant epitopes restricted by the HLA-B*58:01 allele. Importantly, these high-avidity TCRs were not enriched for specific V gene usage and demonstrated enhanced antigen sensitivity. Conclusions: Our findings highlight the critical role of antigen exposure duration prior to ART-mediated viral suppression in shaping the avidity of virus-specific T cells. These insights are important for developing strategies to enhance immune responses against HIV-1 through vaccination and other therapeutic interventions, advancing efforts toward a functional cure for HIV. Low Post-ART SIV Viral Load Set Point Associated With Enhanced Lymph Node CD8+ T-Cell Proliferation Gina Borgo 1 , George Gruenhagen 1 , Benjamin Bimber 2 , Shayleen Singh 1 , Steven G. Deeks 1 , Louis Picker 2 , Afam Okoye 2 , Rachel Rutishauser 1 1 University of California San Francisco, San Francisco, CA, USA, 2 Oregon Health and Science University, Portland, OR, USA Background: Identifying immunologic features that correlate with control of HIV/SIV after antiretroviral therapy (ART) is stopped will inform the design of improved curative strategies for HIV. Here, we characterized features of lymph node (LN) CD8+ T cells in a cohort of 10 rhesus macaques infected i.v. with SIVmac239 that achieved a range of SIV plasma viral load (pVL) set points after analytic treatment interruption (ATI; range 65-225,000 c/mL). Methods: To identify CD8+ T cell features that correlate with subsequent post-ATI pVL set point, we performed spectral flow cytometry including SIV specific class I tetramers on peripheral LN mononuclear cells collected pre-ATI, and at 7/8 and 15 days post-ATI (median pVL 32 and 10,600 c/mL, respectively). We also performed single cell RNA/TCR (scRNA/TCRseq) sequencing on sorted total live LN cells from a subset of animals. Results: Prior to stopping ART, animals with low pVL set points had a higher frequency of cycling (Ki67+) CD8+ T cells within the central memory (Tcm: CD95+CD28+CCR7+), transitional memory (Ttm: CD95+CD28+CCR7-), and follicular-like (CXCR5+PD-1+) subsets (10.4% vs 6.1% p=0.01, 7.2% vs 4.7% p=0.02, and 7.5% vs 4.0% p=0.01, respectively). Low pVL set point also correlated with a higher frequency of TCF-1+ Ttm pre-ATI (Spearman’s r=-0.77, p=0.01). After treatment interruption, the frequency of Ki67+ Tcm at d7/8 post-ATI was negatively correlated with the level of SIV RNA measured in the same LN (r=-0.83, p=0.02). By scRNA/TCRseq, animals that achieved low pVL set points had a higher frequency of naïve/early memory CD4+ and CD8+ T cells post-ATI, as well as a higher frequency of an effector-like cluster of CD8+ T cells expressing CCL5 , CTSW , GZMM , GZMK , and NKG7 at d7/8 post-ATI. Conclusions: We found that animals with lower post-ATI pVL set points both start out with and then continue to maintain into early rebound a larger fraction of actively cycling CD8+ T cells in the LN.

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Duration of Viremia Modulates Antigen Sensitivity of HIV-Specific T-Cell Receptors Funsho Ogunshola 1 , Nishant K. Singh 2 , Vincent Butty 2 , Anurag R. Mishra 1 , Liza Vecchiarello 1 , Kate B. Juergens 1 , Zacharia Habte 1 , Alicja Piechocka-Trocha 1 , Kavidha Reddy 3 , Brandon J. Dekosky 1 , Gaurav D. Gaiha 1 , Krista Dong 1 , Thumbi Ndung'u 3 , Michael Birnbaum 2 , Bruce Walker 1 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 2 Massachusetts Institute of Technology, Cambridge, MA, USA, 3 Africa Health Research Institute, Mtubatuba, South Africa Background: Virus-specific CD8 + T cells are important for controlling chronic viral infections such as HIV. However, it remains unclear how the cumulative duration of antigen exposure following acute infection before complete viral suppression via ART impacts the quality of the memory T cell repertoire. In

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CROI 2025