CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

immunophenotyping and transcriptomic analysis via scRNA-seq (Seq-well), we characterized defining features of the "putative cure" individuals compared to the other groups. Results: We show that ‘putative cure’ children closely resemble pediatric slow progressors (PSPs), with decreased CCR5 and CD73 expression on CD4+ T-cell memory subsets, associated with poor viral entry and smaller viral reservoirs. On CD8+ T-cell memory subsets, this similarity with PSPs is recapitulated via early, albeit transient PD-1 expression. Using scRNA-seq, geneset enrichment analysis and weighted gene correlation network analysis, we demonstrate unique TNFα and NFkB-dependent immune activation in conjunction with an absence of type-I IFN immune activation when compared to other children LWH. Conclusions: These findings indicate that pediatric “putative cure” is linked to a distinct immune combination, leveraging the advantages of TNFα-driven immune activation whilst circumventing type-I IFN specific resistance, plus patient-specific protective features limiting the potential for HIV entry via CCR5 and establishment of latent virus at early time points via CD73. Targeting these potentially optimal immune signatures or augmentation of these distinct inflammatory pathways may ultimately inform future therapeutic developments in achieving HIV cure/remission. The figure, table, or graphic for this abstract has been removed. 1040 Germline-Targeting SOSIP Trimer Immunizations Reduced Post-Rebound SHIV Loads in Infant Macaques Aiquan Chang 1 , Nicole Soo 1 , Tracy Ordonez 2 , Olusola Omonije 1 , Shilpi Pandey 2 , Genevieve G. Fouda 1 , Ann Hessell 2 , Mauricio A. Martins 3 , Nancy L. Haigwood 2 , Sallie Permar 1 , Ria Goswami 1 1 Weill Cornell Medicine, New York, NY, USA, 2 Oregon Health and Science University, Portland, OR, USA, 3 The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL, USA Background: Globally, >1.4 million children are living with HIV. Life-long ART adherence predisposes children to drug-associated complications, necessitating development of adjunctive therapies that can achieve drug-free viral suppression. Our group recently demonstrated development of VRC01-like broadly neutralizing antibody (bNAb) precursor responses in pediatric rhesus macaques (RMs) upon immunization with a germline-targeting native-like HIV SOSIP trimer. In this study, our objective is to determine the impact of germline-targeting SOSIP trimer immunization of SHIV-infected infant RMs on viral rebound post-ART interruption (ATI). Methods: Infant RMs (n=11) were orally challenged with SHIV SF162P3 and started on ART at 1 week post-infection (wk pi). Of these, 5 RMs were immunized with 4 doses of BG505 GT1.1 SOSIP+3M052-SE, followed by 3 doses of autologous SF162P3 SOSIP+3M052-SE, and 6 RMs did not receive any immunizations (controls). ART was interrupted at 30 wk pi for controls and 47 wk pi for immunized animals. Plasma viral load (PVL), HIV-trimer-specific IgG, and autologous virus-neutralizing antibodies were measured longitudinally. Finally, using a virus that is neutralized by germline-reverted forms of VRC01, the development of CD4bs-specific bNAb precursors in plasma was evaluated. Results: While there was no difference in the time to viral rebound in control [median(range) wks: 2(1-3) wks] vs. immunized RMs [Median(range) wks: 2(1.5-3) wks], 1 RM did not experience viral rebound and 1 achieved plasma viral control 5 wks post-rebound in the immunized group. Compared to controls, the immunized group had a 22.9 fold lower post-rebound peak PVL (p=0.004) and 43.9 fold lower post-ATI PVL-AUC 0-15 wk (p=0.004). Immunized animals had higher magnitude and more durable BG505 GT1.1 SOSIP-specific and SF162 trimer-specific plasma IgG compared to control RMs. The GT1-specific (r=-0.62; p=0.04) and SF162-specific (r=-0.88; p<0.001) IgG levels at ATI inversely correlated to post-ATI PVL-AUC 0-15 wk . Importantly, none of the controls and 2/5 immunized animals developed VRC01-class bNAb precursor response, and the RM with the highest level of autologous virus-neutralizing antibody at 2 weeks post-ATI did not experience viral rebound. Conclusions: Germline-targeting native-like HIV env trimer immunization of SHIV-infected infant RMs, induced potent HIV-specific antibody levels and CD4bs-specific bNAb precursor response resulting in dampened viral replication for 15 weeks post-ATI.

1041 Immune Correlates of Viral Rebound During Broadly-Neutralizing Antibody Treatment in Children Melanie Lancien 1 , Aischa Niesar 1 , Seohyun Hong 1 , Leah Carrere 1 , Ajibola Gbolahan 2 , Terence Mohammed 2 , Shahin Lockman 3 , Ce Gao 1 , Sikhulile Moyo 2 , Bryan S. Nelson 3 , Michael Hughes 3 , Xu G. Yu 1 , Daniel Kuritzkes 4 , Roger Shapiro 3 , Mathias Lichterfeld 1 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA, 2 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Brigham and Women's Hospital, Boston, MA, USA Background: Determining immunologic correlates that may be associated with virologic suppression while on alternate or curative HIV therapy is a priority for children. We longitudinally investigated immune responses among participants in the Tatelo Study with and without virologic failure during 6 months of dual bNAb-treatment after ART interruption. Methods: Using multiparametric spectral flow cytometry we analyzed innate and adaptive immune cell populations at two time points: 1) the start of bNAb only treatment and 2) at ART reinitiation after six months or upon viral rebound. We correlated immunological findings with viral reservoir characteristics obtained through FLIP-seq and MIP-seq. Results: Of 25 participants aged 2-5 years who received VRC01LS plus 10-1074 dual-bNAb treatment, 11 maintained viral suppression (controllers) and 14 rebounded (rebounders). Controllers exhibited a trend toward higher proportion of CD56 dim CD16 dim NK cells and lower proportion of CD56 pos CD16 - NK cells compared to rebounders, at both time points. The percentage of NK cells expressing the inhibitory receptor KIR2DL1 tended to be higher in rebounders at the start of bNAb-only-treatment (p=0.09) and at ART reinitiation (p=0.04). This was also true for the subset of KIR2DL1 + NKG2A - NKp46 - NKp30 - NK cells at the start of bNAb-only-treatment (p=0.05). Additionally, the proportion of cells expressing KIR2DL1 positively correlated with the frequency of intact proviruses (p= 0.008) and with a shorter time to rebound (p=0.01). The higher expression of KIR2DL1 in rebounders was paired with an enrichment of HLA-C allotypes (p=0.03) that display elevated surface expression and serve as preferred inhibitory ligands for KIR2DL1. The proportions of NKG2A-expressing NK cells at the start of bNAb-only-treatment were positively correlated with time to rebound (p=0.012) and inversely correlated with intact reservoir size at both time points (p=0.014). Frequencies of HIV-1-specific T cells were low at both time points, did not differ between controllers and rebounders, and did not correlate with viral reservoir size. Conclusions: Specific NK cell responses at the beginning of bNAb-only treatment were associated with viral rebound, the kinetics of rebound, and the intact viral reservoir size. HIV-1 specific T cell responses were low in this group of early-treated children and differences could not be identified between controllers and rebounders. 1042 HIV-Specific T-Cell Dynamics in Acute-Treated, Chronic-Treated, and Elite Controller People With HIV Alicer K. Andrew 1 , Xiaoyu Luo 1 , Jason Neidleman 1 , Michael Peluso 2 , Rebecca Hoh 2 , Steven G. Deeks 2 , Sulggi Lee 2 , Steven Yukl 2 , Nadia R. Roan 1 1 Gladstone Institutes, San Francisco, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA Background: Early initiation of ART can preserve immune function and is associated with increased incidence of post-treatment control of HIV, yet differences in HIV-specific immune responses between people with HIV (PWH) who initiated ART during acute vs. chronic infection are poorly defined. The extent to which immune responses in early- and late-treated PWH differ from those of elite controllers (ECs)–who exhibit ART-free control of HIV–has also not been fully evaluated. We used CyTOF to compare the frequencies, phenotypes,

Poster Abstracts

CROI 2025 333