CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1038 Negative HIV Serology in Children Treated Early Reflects a Unique Immunological Profile Florence Buseyne 1 , Caroline Charre 2 , Josiane Warszawski 3 , Jerome Le Chenadec 4 , Thomas Montange 1 , Ingrid Fert 1 , Adeline Duretz 2 , Elise Gardiennet 2 , Stéphane Blanche 5 , Catherine Dollfus 6 , Marie-Dominique Tabone 6 , Albert Faye 7 , Pierre Frange 5 , Véronique Avettand-Fenoël 8 , for the ANRS-MIE-EP59-CLEAC Study Group 1 Institut Pasteur, Paris, France, 2 Cochin Hospital, Paris, France, 3 Hôpital Bicêtre, Le Kremlin-Bicetre, France, 4 Université Paris-Saclay, Gif-sur-Yvette, France, 5 Hôpital Necker, Paris, France, 6 Hôpital Armand-Trousseau, Paris, France, 7 Robert–Debre Hospital, Paris, France, 8 Centre Hospitalier Régional d'Orléans, Orléans, France Background: Negative HIV serology in children treated early is thought to result from low exposure of the immune system to antigenic stimulation provided by HIV replication. This serological profile might be used to identify pediatric patients eligible for HIV cure strategies. We, thus, aimed to characterize parameters associated with negative HIV serology in children who initiated ART early. Methods: The present analysis included children (aged 5-12 years) from the French ANRS-EP59-CLEAC study who initiated combined antiretroviral therapy (cART) before six months of age, reached virological success (HIV-RNA < 400 copies/mL in the 24 months after cART initiation), did not subsequently experience viral rebound > 400 copies/mL, and had HIV RNA < 50 copies/ mL at the time of the study. The presence of HIV-1 antibodies was determined using the EIA VIDAS HIV DUO ULTRA test (Biomérieux). Blood lymphocytes were quantified by flow cytometry. PBMCs were stimulated by a TLR7/8 agonist and IL-2 to assess the expansion of B lymphocytes producing HIV-specific antibodies. Fisher and Mann-Whitney tests were used to analyze variables associated with negative HIV serology. Results: Seventeen children met the selection criteria: four males, median age 9 [Interquartile range: 5.5; 11] years, and CD4 T-cell count 1090 [735; 1388] cells/ µl. Seven participants had negative HIV serology (seronegative, SN, 41%) and 10 had positive HIV serology (seropositive, SP, 59%). SN children tended to be younger at cART initiation than SP children (14 vs 97 days, P = 0.06). At the time of the study, surrogate markers of past HIV exposure did not distinguish SN from SP children (total HIV DNA, 1.9 [1.4; 2.2] vs. 2.2 [1.2; 2.5], log 10 copies/10 6 PBMCs, P = 0.64, plasma HIV-1 p24 detection: 25% vs 38%, P = 0.67). SN children had a higher percentage of circulating follicular CXCR5+CCR4- CD8 T EM lymphocytes than SP children (3.1% [2.0; 3.2] vs 1.3% [0.7; 2.0], P = 0.01). Although rarely detected, HIV-specific B cells were present in both SN and SP children. Conclusions: Among children over the age of five years with limited exposure to HIV replication, negative HIV serology could not be attributed to B lymphocyte defects. Rather, it was associated with expanded circulating follicular CD8 T lymphocytes, previously reported to have high antiviral activity. Thus, negative HIV serology may be a biomarker of a good potential for HIV immune control in the context of future HIV cure strategies. 1039 Distinct Innate Immune-Driven TNFa Pathway Is Linked With Durable ART-Free Aviremia in Pediatric HIV Nicholas Lim 1 , Gabriela Z. L. Cromhout 2 , Philip Goulder 1 , Emily Adland 1 , Alex K. Shalek 3 , Nomonde Bengu 2 , Vinicius Vieira 1 1 University of Oxford, Oxford, UK, 2 Africa Health Research Institute, Mtubatuba, South Africa, 3 Massachusetts Institute of Technology, Cambridge, MA, USA Background: Mechanisms underlying sustained ART-free HIV cure/remission remain elusive. Very-early ART-treated children LWH after vertical transmission may have a high potential for cure/remission due to the tolerogenicity of early life immunity. We here evaluate a group of children LWH maintaining ART-free undetectable levels of HIV viral RNA and DNA termed “ putative cure” children. Previous publications in our group reveal that these children possess transmitted viruses with low replicative capacity, typically associated with increased type-I IFN resistance. Methods: In KwaZulu-Natal, South Africa, we have followed from birth a cohort of 316 children LWH after in-utero vertical transmission. These children were categorized into 5 groups: ‘putative cure’ children, who maintained aviremia despite unscheduled ART discontinuation, determined by history and measurement of plasma ART levels by LC-MS/MS; 3 groups of HIV-infected children with 0, 1-2, or > 2 blips/spikes of plasma viraemia detected over the course of follow up of >36m (Groups 1-3, respectively); and healthy, HIV-negative controls. Employing flow cytometry for surface-level

potential candidates for ART-free virological control should consider both HIV specific antibody and reservoir size.

1037 Baseline Viral Load Impacts Premature Aging in Infants With Perinatally Acquired HIV in EARTH Cohort Maria Raffaella Petrara 1 , Elena Ruffoni 1 , Giuseppe Rubens Pascucci 2 , Elena Morrocchi 3 , Francesco Carmona 1 , Nicola Cotugno 2 , Paolo Rossi 2 , Silvia Giunco 1 , Carlo Giaquinto 1 , Paolo Palma 2 , Anita De Rossi 1 , for the EPIICAL Consortium 1 University of Padova, Padova, Italy, 2 Bambino Gesu Children's Hospital, Rome, Italy, 3 University of Rome Tor Vergata, Rome, Italy Background: The aim of this study is to assess the impact of baseline viral load on the premature aging process in infants with perinatally acquired HIV (PHIV), enrolled in the Early Anti-Retroviral Treatment in HIV children (EARTH) cohort. Methods: Thirty-six ART-naïve PHIV infants, with a median age of 1.6 (1.3-2.5) years at enrollment, were stratified in two groups based on plasma viremia at enrollment: group 1 (<25 percentile of Log2 HIV-RNA) and group 2 (>75 percentile of Log2 HIV- RNA). The immune aging profile, including activated, senescent and exhausted T cells, were analyzed by flow cytometry. Relative telomere length and HIV-DNA levels in peripheral blood mononuclear cells (PBMC) were measured by real-time PCR and droplet digital PCR, respectively. Statistical analyses were performed using SigmaPlot software. Results: Plasma viremia significantly correlated with HIV-DNA in PBMC (r=0.525, p=0.003). Baseline levels of HIV-DNA levels in PBMC were significantly higher in group 2 than in group 1 (1159 [617-4426] vs 89 [9-1607] copies/106 PBMC, p=0.011). Similarly, group 2 had higher percentages of activated (CD38+HLA-DR+), senescent (CD27-CCR7-CD45RA+CD28-CD57+) and exhausted (PD-1+) CD4 and CD8 T cells than group 1 (Relative Telomere lengths were significantly shorter in group 2 than in group 1 (1.82 [1.68-1.90] vs 1.93 [1.78-2.26], p=0.020). Conclusions: Higher baseline viral load strongly correlated with HIV-DNA levels in PBMC and led to increase immune activation and senescence, thus suggesting that baseline plasma viremia impacts the aging process in PHIV starting from very early age.

Poster Abstracts

CROI 2025 332