CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

the existence of antigen-specific NK cells, we established a novel procedure for single-cell clonal expansion of NHP NK cells, which maintain a conserved NHP NK cell phenotype of CD3- NKG2A/C+ CD16+ CD56+ following expansion. Autologous peptide-loaded BLCL elicited a broad-spectrum of rhNKCL cytotoxic responses, with higher response for SIV ENV-derived peptide. Conclusion: In summary, these findings elucidate antigen-specific NK responses during SIVmac infection dependent on MHC-E-mediated SIV-derived peptide presentation. Also, we introduced a ground-breaking method for the clonal expansion of single NK cells in RM. This study may provide valuable insights into antigen-specific NK cells, including the establishment of epigenetic, metabolic, transcriptional, and phenotypic profiles. Such insights could be leveraged to enhance antiviral NK cell activity in future vaccine strategies and cell therapies. [18F]F-AraG PET Imaging Reveals Unique Tissue T-Cell Activation Patterns Across HIV Infection States Basic Science: Timothy J Henrich 1 , Robert Flavell 1 , Michael J. Peluso 1 , Kofi Asare 1 , Maya Aslam 1 , Emily Fehrman 1 , Meghann C. Williams 1 , Viva Tai 1 , Rebecca Hoh 1 , Youngho Seo 1 , Jelena Levi 2 , Steven G. Deeks 1 , Henry VanBrocklin 1 1 University of California San Francisco, San Francisco, CA, USA, 2 CellSight Technologies, San Francisco, CA, USA Background: Non-invasive tools that can test the hypothesis that abnormal T cell activation in various tissues differs across HIV-1 disease states are needed. We used [18F]F-AraG, a small-molecule PET tracer highly specific for activated T cells (CD8>CD4), to compare whole-body T cell activation states in people with HIV (PWH) on and off ART, and experiencing post-intervention control (PIC), compared to uninfected control participants. Methods: [18F]F-AraG (~5mCi) was administer i.v. to13 PWH (12 male, one transgender female; 8 on ART, 2 viremic, 3 PIC following combination immunotherapy) and 6 uninfected volunteers [3 male, 3 female]) followed by whole-body PET-MR imaging. Maximum and mean standardized uptake values (SUVmax/mean) were calculated for regions of interest (ROI) and compared across cohorts using non-parametric tests adjusted for multiple comparisons. Results: We observed significantly higher [18F]F-AraG SUVmean and SUVmax in many tissues (nasal turbinates, axial bone marrow, distal spinal cord/ cauda equina, lung parenchyma, pulmonary artery, and rectal wall) in PWH comparted to uninfected controls (all P<0.05; Fig 1). Elevated T cell activation was evident even among those on ART (VL<40 c/mL) in these ROI with the exception of lung tissue. Interestingly, tracer uptake was significantly lower in inguinal lymph nodes from all PWH, PWH on ART, and PTC, compared to uninfected controls (all P<0.02). PWH experiencing PIC had significantly higher SUVmean/max in pulmonary artery, axial marrow and rectal wall (SUVmean) compared to uninfected controls, but not in lungs or nasal turbinates. There were no significant differences in tracer uptake in male versus female control participants in any ROI and analyses of all PWH excluding female controls yielded similar results. Conclusion: This study is the first to show persistent T cell activation in bone marrow, pulmonary artery, and nasal and gut tissue across a range of HIV-1 disease states using non-invasive PET-MR imaging. Interestingly, T cell activation in lung parenchyma appears to be driven by viremic PWH, and all PWH had lower T cell activation in inguinal lymph nodes compared to uninfected controls, regardless of disease phenotype. We previously observed high uptake of a HIV gp120-specific bnAb PET tracer in inguinal lymph nodes from viremic and ART-suppressed PWH suggesting that combinations of non invasive imaging tools may play an important role in determining the interplay between host immune responses and viral persistence.

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Oral Abstracts

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Biomarker Signatures in Phase Ib Study With PD-1 Inhibitor, Budigalimab, in PLWH Undergoing ATI Preethi Krishnan 1 , Ana Gabriela Pires Dos Santos 1 , Harsh Sharthiya 1 , Rakesh L. Tripathi 1 , Thomas J. Reisch 1 , Tanaya Vaidya 1 , Fei Zhou 1 , Moti Ramgopal 2 , Meri Oliva 1 , Aparna Vasanthakumar 1 , Daniel E. Cohen 1 , Jean-Pierre Routy 3 , Patrick K. Dorr 1 1 AbbVie, Inc, North Chicago, IL, USA, 2 Midway Immunology and Research Center, Fort Pierce, FL, USA, 3 McGill University Health Centre Research Institute, Montreal, Canada Background: HIV infection is a major global health problem with ART-free viral control remaining an unmet need. PD-1 blockade offers a promising approach to help address this. We conducted a phase 1b randomized double-blind study (NCT04223804) with an investigational PD-1 inhibitor, budigalimab, in people living with HIV-1 (PLWH) and included planned analytical treatment interruption (ATI) enabling exploratory efficacy and biomarker analyses. Budigalimab was well tolerated, and ART-free viral suppression was observed in a subset of participants. Preliminary exploratory biomarker analyses characterizing the impact of treatment and ATI are presented. Methods: Safety, pharmacokinetics and pharmacodynamics were examined across multiple intravenous doses of budigalimab (2−10 mg; n=31) and placebo (n=10). Exploratory analyses examined off-ART viral load kinetics, PD-1 receptor saturation, T cell activation and proliferation, plasma cytokines and chemokines, and genome-wide transcriptomic abundances. Results: High peripheral PD-1 receptor saturation was observed for a period of approximately 10 weeks with 10mg Q2Wx4 doses of budigalimab. Six of 9 participants who completed the 10mg Q2Wx4 doses administered during ATI had delayed viral rebound and/or off-ART viral control (HIV-1 RNA <1000 copies/ mL), with 2 participants maintaining viral control off ART at <200 copies/mL for over 29 weeks. None of the participants receiving placebo demonstrated this viral load kinetic profile. Increased CD8+ T cell activation was observed and correlated with viral load during ATI. Participants with high viral load during ATI displayed differential transcriptomic trajectories as compared to the profile in participants with low viral load (HIV-1 RNA <1000 copies/mL). Budigalimab treatment was associated with more frequent increases in plasma CXCL9 and CXCL10 during ATI as compared to placebo, though there was no association of these markers with treatment response. A trend in budigalimab-mediated

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CROI 2024 v CROI 2021