CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

response as well as the contribution of humoral and innate immunity in post treatment control. Time to Viremia and Frequency of Post-Treatment Control Among 382 “Placebo-Treated” ATI Participants Jesper D. Gunst 1 , Jesal Gohil 2 , Jonathan Li 3 , Tae-Wook Chun 4 , Beatriz Mothe 5 , Linos Vandekerckhove 6 , Timothy Schacker 7 , Luis J. Montaner 8 , Javier Martinez Pìcado 9 , Ruxandra Calin 10 , Antonella Castagna 11 , Felipe Garcia 12 , Rob A. Gruters 13 , Ole Søgaard 14 , Sarah Fidler 2 1 Aarhus University Hospital, Aarhus, Denmark, 2 Imperial College London, London, UK, 3 Brigham and Women's Hospital, Boston, MA, USA, 4 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 5 Fundació Lluita contra la SIDA, Badalona, Spain, 6 HIV Cure Research Center, Ghent University, Ghent, Belgium, 7 University of Minnesota, Minneapolis, MN, USA, 8 The Wistar Institute, Philadelphia, PA, USA, 9 IrsiCaixa, Badalona, Spain, 10 Hôpital Pitié-Salpêtrière, Paris, France, 11 IRCCS San Raffaele Scientific Institute, Milan, Italy, 12 Universitat de Barcelona, Barcelona, Spain, 13 Erasmus University, Rotterdam, Netherlands, 14 Aarhus University, Aarhus, Denmark Background: There is a global need to explore novel interventions conferring sustained HIV control without antiretroviral therapy (ART). The only current strategy to test efficacy is through an analytical treatment interruption (ATI). Inclusion of ‘placebo’ controls in future clinical trials poses ethical, logistical, and economic challenges and might be unnecessary if sufficient up-to-date data exists from non-intervention cohorts of people with HIV (PWH) who stop ART. To understand viral rebound dynamics and rates of post-treatment control (PTC) in the absence of any intervention, we undertook an individual-level participant data meta-analysis on time to viremia after ATI. Methods: We included data from clinical studies with ≥5 separate available plasma HIV RNA viral load (pVL) measurements within the first 84 days post-ATI in PWH receiving either placebo or no intervention. Eligible prospective studies were identified through literature search on PubMed. Early-ART was defined as ART initiation within 6 months of HIV acquisition; others were classified as late-ART or unknown. Our data was used as reference to calculate the number of participants needed in either a single arm or 2-group randomized controlled trial design with a power of 90% to detect specified prolonged time to viremia or proportion of PTC at a 5% significant level, one-sided. Results: In total, 24 studies with 382 individuals were included. Median age was 42 years, 91% male, 75% white, 45% received early-ART. Median time to pVL >50, >400, and >10,000 copies/mL was 16 days (interquartile range [IQR]:13–25), 21 (IQR:15–28), and 32 (IQR:20–35), respectively. PTC defined as pVL <50 copies/mL at day 84 occurred in 4% (n=14) of participants (6% for early-ART and 1% for late-ART). If the expected outcome of an intervention is a frequency of 25% PTC among early-ART participants, 36 individuals would need to be included in a single arm design and 128 individuals in a 2-group randomized trial design. Conclusions: Sustained control of pVL <50 copies/ml after 84 days off ART is rare in PWH who stop therapy, especially in those starting ART late. When designing future interventional HIV cure/remission trials, these findings help inform study size and design, potentially removing the need for a placebo arm thereby minimizing unnecessary risks to participants and their partners, while optimising resources. Characterization of HIV Antibodies and p24 Antigen During Analytical Treatment Interruption Clara Di Germanio 1 , Brendan Balasko 1 , Patricia Villaflor 1 , George Noutsios 2 , Catalina Esteban-Christen 2 , Alfredo Villarreal 2 , Jonathan Li 3 , Davey Smith 4 , Steven G. Deeks 5 , Ronald J. Bosch 6 , Rajesh T. Gandhi 7 , Philip J. Norris 1 , Michael P. Busch 1 1 Vitalant Research Institute, San Francisco, CA, USA, 2 Bio-Rad, Seattle, WA, USA, 3 Brigham and Women's Hospital, Boston, MA, USA, 4 University of California San Diego, La Jolla, CA, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 Harvard TH Chan School of Public Health, Boston, MA, USA, 7 Harvard Medical School, Boston, MA, USA Background: Characterization of HIV humoral immunity has provided insights into the role of HIV antibodies (Ab) in controlling HIV and as biomarkers of HIV replication during infection and antiretroviral therapy (ART) use. The aim of this study was to determine if HIV Ab and antigen (Ag) quantitation could detect anamnestic induction of humoral immunity prior to detectable plasma viral load (VL) rebound following analytical treatment interruption (ATI), and if longitudinal measurements of p24 Ag/Ab provide insights into post-rebound viral replication. Methods: Longitudinal plasma samples from 41 ACTG A5345 study participants who started ART during chronic or early phase of infection and underwent ATI

(88% males, 485 samples; mean 12/participant), previously characterized for plasma VL rebound kinetics and virological correlates of time to rebound, were analyzed using the Ortho Vitros HIV1+2 (p24/env Ab) and Combo (p24 Ag/env Ab), the Sedia Limiting Ag Avidity and the Bio-Rad BioPlex2200 HIV Ag-Ab (p24 Ag/HIV M/O/2 Ab)assays which discriminates p24 Ag and Ab signals, with and without a denaturation step to separate p24 Ag-Ab immune complexes (IC). Results: Neither Ab nor Ag increased prior to VL rebound. 31 of 41 (76%) participants (both chronic and early treated) showed increased Ab levels (2 timepoints >10% from baseline) following RNA rebound peak and declined after restarting ART. The 8 participants who did not show increased seroreactivity had higher Ab levels at ATI initiation (mean Ortho Combo S/CO 237 vs 154, p<0.001 one-way ANOVA). Early-treated participants had lower Ab levels at ATI initiation (early vs chronic-treated S/CO 80 vs 173, p=0.0004), but larger fold increases during ATI (1.6 vs 1.2-fold, p=0.002) (Fig.1). Two participants with post-treatment control had progressive increase in seroreactivity that paralleled the slow/intermittent increases in VL. p24 Ag was not detectable without the denaturation step; however, after IC dissociation, p24 Ag reactivity became positive in samples with VL >10 4 RNA copies/mL and correlated with the VL levels across the longitudinal series (Spearman r=0.89). Conclusions: Commercial HIV serological assays detected an anamnestic Ab induction following VL rebound after ATI in 76% of cases. p24 Ag was detectable at rebound VL>10 4 RNA copies/mL only following IC dissociation. Longitudinal p24 Ag/Ab quantitation provides insights into post-rebound viral replication and impact of ART reinitiation and could be useful for monitoring of ATIs.

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Poster Abstracts

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Post-Treatment HIV Controllers Exhibit Reduced Plasma Markers of Inflammation and Metabolic Stress Leila B. Giron 1 , Qin Liu 2 , Jianyi Ding 2 , Xiangfan Yin 2 , Alan Landay 3 , Jeffrey M. Jacobson 4 , Jonathan Li 5 , Mohamed Abdel-Mohsen 1 1 Northwestern University, Chicago, IL, USA, 2 The Wistar Institute, Philadelphia, PA, USA, 3 University of Texas Medical Branch, Galveston, TX, USA, 4 Case Western Reserve University, Cleveland, OH, USA, 5 Brigham and Women's Hospital, Boston, MA, USA Background: A rare subset of people with HIV (PWH) on antiretroviral therapy (ART), known as post-treatment controllers (PTCs), can maintain viral suppression for extended periods after treatment interruption (TI). The mechanisms underlying this clinically valuable phenotype remain unclear and are likely multifactorial, necessitating further comprehensive analysis. Methods: Pre-TI levels of 247 inflammation and immunomodulatory markers were measured in the plasma of 14 PTCs and 27 matched post-treatment non controllers (PTNCs) using a multiplex Nucleic acid Linked Immuno-Sandwich Assay (NULISA). PTCs sustained virologic control for ≥24 weeks, maintained plasma viral loads ≤400 copies/ml for at least two-thirds of time points, underwent plasma drug level testing, and had no evidence of spontaneous control before ART initiation. The two groups were matched for sex (p=0.41), age (p=0.75), ethnicity (p=0.74), ART initiation timing (p=0.69), ART duration (p=0.5), and pre-TI CD4 count (p=0.92). Results: A distinct set of pre-TI markers correlated with the likelihood of achieving the PTC phenotype. Notably, pre-TI levels of FGF21, a hormone regulating sugar and lipid metabolism with anti-inflammatory and anti metabolic stress effects, was significantly higher in PTCs than PTNCs (p=0.004). FGF21 exhibited a significant odds ratio (OR=1.64; p=0.04) for predicting the PTC phenotype in a logistic model. A predictive model using FGF21 alone demonstrated 78% accuracy, 79% sensitivity, 78% specificity, and an area under the curve (AUC) of 0.77. In addition, CCL4, a chemokine promoting immune surveillance (OR=3.5; p=0.03); erythropoietin (EPO), which exhibits anti-inflammatory properties (OR=2.4; p=0.04), and CNTF, which supports neuronal health and maintains gut barrier integrity (OR=1.7; p=0.048), all

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