CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

CD45RO+) subsets. HIV-1 proviruses in CD4 cell subsets and unsorted PBMCs were characterized by 5'LTR-to-3'LTR PCR single-genome amplification and direct amplicon sequencing. Results: Sequencing of 1,174 HIV-1 proviruses in the three CD4 cell subsets and PBMCs identified 78 expanded defective HIV-1 provirus clones, each harboring distinct defective provirus barcodes. 23 of the 78 clones persisted for ≥3 yrs (median: 6 yrs, range: 3-10 yrs). The highest number of provirus-barcoded clones was found in the CM pool (n=28) followed by the EM (n=25) and NA (n=13) pools, corresponding to 61%, 79%, 30% of the total provirus sequences detected in CM, EM and NA cells, respectively (Figure). One of the dominant clones (the pink-colored sections of the bars in the figure) is a 6 kb HIV-1 provirus with hypermutations. It was first detected in CM cells and 3 yrs later in NA cells. In addition, clonal conversions from EM to CM (2 provirus-barcoded clones) and reversions from CM to NA (5 provirus-barcoded clones) were observed. Conclusions: The strategy of using expanded defective HIV-1 provirus clones as a novel “barcode” enables high-resolution insights into T-cell dynamics and demonstrates the durability of clonal populations in each subset. In contrast to the current dogma of effector memory populations being short-lived, these data demonstrated that they are able to persist in vivo for several years or more.

Cohort (JHHCC, n=1). The average of ~5 replicates per sample-timepoint was used. Mann Whitney U test or chi squared test were used for comparisons. Results: Consistent with design, no significant differences were seen between SoIRs and controls by age at ART start/restart (median 45 vs 42, respectively), race, sex (10% vs 15% female sex), CD4+ nadir (median 29 vs 31), HCV seropositivity (15% each), or ever-IV drug use (21% vs 18%). The median time from ART start or restart to sample collection was 22 months in each group. The median CD4+ count 5 yr after ART start/restart was 265 among SoIRs vs 650 among controls. There were no significant differences between SoIRs and controls in the frequency of intact or defective proviruses among circulating CD4+ T cells (Figure). Conclusions: We demonstrate here that the frequency of HIV-infected CD4+ T cells - whether harboring intact or defective HIV proviruses – in the first few years after ART initiation does not associate with future SoIR status. Further research is needed to understand the biological contributors to poorer outcomes in SoIRs.

Poster Abstracts

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Impact of ART Initiation on HIV-1 Soluble gp120 Levels and CD4 Counts in PWH Mehdi Benlarbi 1 , Jonathan Richard 2 , William D. Tolbert 3 , Marzena Pazgier 3 , Jean Pierre Routy 4 , Madeleine Durand 2 , Andrés Finzi 2 1 Université de Montréal, Montreal, Canada, 2 Centre de Recherche du CHUM, Montreal, Canada, 3 Uniformed Services University of the Health Sciences, Bethesda, MD, USA, 4 McGill University Health Centre Research Institute, Montreal, Canada Background: While antiretroviral therapy (ART) suppresses viremia to undetectable levels, people with HIV (PWH) show signs of chronic inflammation and immune dysfunction. Persistent viral antigenic stimulation may contribute to this phenomenon. In a cross-sectional study of ART-treated PWH with undetectable viremia, we recently reported that soluble gp120 (sgp120) was associated with markers of inflammation and immune dysfunction. However, the dynamics of plasmatic sgp120 levels, its association over time with inflammation, immune dysfunction and how this is affected by ART remains unclear. Methods: To evaluate the dynamics of sgp120, we performed a longitudinal assessment of sgp120, anti-Env antibodies (Abs) including those targeting the CD4 binding site (CD4BS), and inflammatory markers associated with HIV-1 infection. We evaluated the association between sgp120 and CD4 count, IL-6, TNF-alpha and Galectin-9. Measures of associations were modelled using generalized least squares (GLS) linear regression with random effects (for repeated measures), with interaction terms between sgp120 levels and i) time period pre/post ART and ii) presence/absence of CD4BS Abs. Results: We included 151 longitudinal samples from 23 PWH taken during primo-infection and up to 4 years post-ART initiation. The mean age of participants was 36.8, 95% were males. 21/23 participants had detectable levels of sgp120 for at least one timepoint. We observed that sgp120 was inversely associated with CD4 cell counts post-ART initiation (beta; -52.17 95%CI -84.64 to -19.70, p=0.002). We did not observe this association pre-ART initiation (beta; -27.10 95%CI -73.93 to 17.94, p=0.23, p-value for interaction 0.38). Of note, anti-CD4BS Abs, known to prevent sgp120-CD4 interaction, modulated the association between sgp120 and CD4 cell counts. Absence of anti-CD4BS Abs strengthened this association (beta; -57.38 95%CI -89.63 to -25.13, p<0.001)

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Similar Intact and Defective HIV Provirus Frequency in Suboptimal Immune Responders and Controls Arianna Romero 1 , Danielle Rigau 2 , Selin Akbas 1 , Richard Moore 3 , Joseph J. Eron 4 , John W. Mellors 5 , Deborah McMahon 5 , Rajesh T. Gandhi 6 , Michael M. Lederman 7 , Steven G. Deeks 8 , Ronald J. Bosch 9 , Robert F. Siliciano 1 , Janet M. Siliciano 1 , Annukka Antar 1 , Constance A. Benson 10 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 New York University Langone Medical Center, New York, NY, USA, 3 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 University of Pittsburgh, Pittsburgh, PA, USA, 6 Harvard Medical School, Boston, MA, USA, 7 Case Western Reserve University, Cleveland, OH, USA, 8 University of California San Francisco, San Francisco, CA, USA, 9 Harvard TH Chan School of Public Health, Boston, MA, USA, 10 University of California San Diego Medical Center, La Jolla, CA, USA Background: A significant percentage of PWH who start or restart antiretroviral therapy (ART) with low CD4+ counts fail to mount a robust CD4+ T cell response despite suppressive ART (suboptimal immune responders, SoIRs). A correlation between the frequency of infected CD4+ T cells and low CD4+ counts on ART has been reported. However, these studies did not control for CD4+ nadir nor time on ART, and it remains unclear whether SoIRs have a higher burden of HIV-infected CD4+ T cells. Methods: We performed the intact proviral DNA assay (IPDA) to quantify estimated frequency of intact and defective HIV proviruses among CD4+ T cells isolated from cryopreserved samples from 62 SoIRs and 67 PWH controls at 1-4 yr post-ART initiation. All participants started/restarted ART with a CD4+ count <200 and maintained virologic suppression for 5+ years. SoIRs were defined as PWH with a CD4+ count <350 at 5 yr post-ART start, controls as PWH with a CD4+ count >500 at 5 yr post-ART start. Controls were selected to match SoIRs on age, race, sex, CD4+ nadir, hepatitis C (HCV) serostatus, ever-IV drug use, and time from ART start to sample collection. Samples and clinical data were obtained from 4 cohorts – ALLRT/ACTG (n=76), the SCOPE cohort (n=45), the Cleveland Immune Failure cohort (CLIF, n=7), and the Johns Hopkins HIV Clinical

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CROI 2025