CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1031 NK Cell KIR Education Is Associated With Low HIV DNA Load in Early ART-Treated Children Nicholas G. Herbert 1 , Gabriela Z. L. Cromhout 2 , Nomonde Bengu 2 , Maria C. Puertas 3 , Javier Martinez-Pìcado 3 , Thumbi Ndung'u 2 , Dimitra Peppa 4 , Philip Goulder 1 1 University of Oxford, Oxford, UK, 2 Africa Health Research Institute, Mtubatuba, South Africa, 3 IrsiCaixa, Badalona, Spain, 4 University College London, London, UK Background: Early ART initiation, low immune activation, and effective anti-HIV NK cell responses have been linked with HIV remission in adults. It has been proposed that these features in combination with early life immunity may favour remission in children living with HIV (LWH). In a cohort of very early ART-treated children in KwaZulu-Natal, South Africa, we here examined the immunogenetic signatures and functional NK cell profile associated with low HIV DNA load and increased HIV cure/remission. Methods: We evaluated a cohort of >300 early-ART-treated children LWH from KwaZulu-Natal, South Africa followed from birth. The cohort included 5 ‘atypical’ children who maintained ART-free aviraemia following unscheduled ART discontinuation. Total HIV DNA was quantified longitudinally as a proxy for reservoir size. NK cell function was assessed via immunophenotypic analysis and stimulation with IL-12/IL-18, K562 cells and Rituximab-coated Raji cells. Results: Low HLA-A expression, favouring KIR-educated NK cells, was associated with low total HIV DNA load at birth and at 9m age (p=0.01 and p=0.01). Also, consistent with adult post-treatment controller (PTC) cohorts, children with ‘protective’ HLA-B alleles (HLA-B*57/58:01/81:01) had 0.5 log 10 higher total HIV DNA loads at birth and 9m (p=0.02 and p=0.04) than those without. High NKG2D expression on CD56 dim NK cells, potentially reflecting heightened inflammation and increased soluble NKG2D ligands such as sMIC-A and sMIC-B, correlated with low HIV DNA (r=-0.51, p=0.005) at 9m age. Following IL-12/IL-18 stimulation, high IFNg production by NKG2A+CD56 dim NK cells was associated with low HIV DNA loads (r=-0.6, p=0.01) at 9m, and spontaneous CD107a production by iKIR+NKG2A-CD56 dim NK cells negatively correlated with HIV DNA load at 9m and 30m (p=0.01 and p=0.01). Unexpectedly, NK cells in the 5 ‘atypical’ children expressed higher iKIR:NKG2A ratio (p=0.05), suggesting a more differentiated NK cell compartment in ‘atypical’ versus ‘typical’ children. Conclusions: These data suggest that an HLA-I signature favouring KIR educated NK cells is associated with low total HIV DNA load in early ART-treated children at birth, implying in utero anti-HIV NK cell activity. This HLA-I signature is consistent with findings from ART-naïve adults, ART-naïve children and adult PTCs. These data also indicate a diverse pattern of CD56 dim NK cell functionality mediating reduced HIV DNA load and increased HIV cure/remission potential in children. 1032 Evolving Expression of Co-Inhibitory Receptors and Plasma Cytokines in Children Living With HIV Hinatea Dieumegard 1 , Mojahidul Islam 2 , Hadiya Johnson 2 , Jade Canape 1 , Madeleine Aby Diallo 1 , Fatima Kakkar 3 , Ari Bitnun 4 , Jason Brophy 5 , Stanley Read 4 , Michael T. Hawkes 6 , Rafick P. Sekaly 2 , Ann M. Chahroudi 2 , Ashish A. Sharma 2 , Hugo Soudeyns 1 , for the EPIC4 Study Group 1 Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada, 2 Emory University, Atlanta, GA, USA, 3 University of Montreal, Montreal, Canada, 4 University of Toronto, Toronto, Canada, 5 University of Ottawa, Ottawa, Canada, 6 BC Children's & Women's Health Centre, Vancouver, Canada Background: HIV disease in children differs from that seen in adults. The objective of this study was to test the association between HIV reservoir size

1030 Long-Term HIV Reservoir Dynamics in Early Treated Thai Children Marta Massanella 1 , Amélie Pagliuzza 2 , Caroline Dufour 2 , Thidarat Jupimai 3 , Supranee Buranapraditkun 3 , Rapisa Nantanee 3 , Julie Mitchell 4 , Mark S. Souza 4 , Piyarat Suntarattiwong 5 , Lydie Trautmann 6 , Remi Fromentin 2 , Thanyawee Puthanakit 7 , Nicolas Chomont 8 , for the HIVNAT209 Study Group 1 IrsiCaixa, Badalona, Spain, 2 Centre de Recherche du CHUM, Montreal, Canada, 3 Chulalongkorn University, Bangkok, Thailand, 4 Oregon Health and Science University, Portland, OR, USA, 5 Queen Sirikit National Institute of Child Health, Bangkok, Thailand, 6 Henry M Jackson Foundation, Bethesda, MD, USA, 7 Chulalongkorn Hospital, Bangkok, Thailand, 8 Université de Montréal, Montreal, Canada Background: Early antiretroviral therapy (ART) and continuous suppression drastically limit the size of the HIV reservoir in adults; however, long-term follow up data on the size and composition of the reservoir in children who initiated ART during the first weeks of life remain limited. We studied the effect of early ART on the long-term dynamics of HIV reservoir markers in Thai children suppressed on ART for up to 10 years. Methods: Forty-nine children with perinatal HIV who initiated ART within a median of 10 IQR [5-14] weeks of life were followed annually (up to 9.9 years). All children received continuous ART during the follow-up period. We quantified total and integrated HIV DNA in CD4 T cells by real-time PCR and measured the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after PMA/ ionomycin stimulation by TILDA. Mixed-effects models were used to measure longitudinal decays in each HIV reservoir marker. Results: Total HIV DNA, integrated HIV DNA and inducible reservoir were detected in all children at high levels before ART initiation (2189 IQR [691 10011], 139 IQR [51-845] and 50 IQR [1-114] infected cells per 106 CD4 T cells, respectively). Longitudinal analysis over a median 4.9 IQR [2.9-7.3] years of ART revealed a biphasic decay of the 3 HIV reservoir markers, with a rapid initial decline followed by a slower decay. During the first-phase decay, similar half lives of total HIV DNA, integrated HIV DNA and TILDA measures were observed (decay of -1.10, -0.68 and -0.96 log10 infected cells/year, respectively, p<0.001 in all cases). During the second phase, HIV reservoir markers remained stable (-0.04, 0.02 and -0.03 log10 infected cells/year, respectively, decay p=ns). Despite no apparent decrease in the size of inducible reservoir, the proportion of participants with detectable TILDAs decreased with time on ART: TILDA+ cells were detected in all children at baseline (100%, n=14), in 60% after 1 to 3 years on ART (n=62), and in less than 40% of the participants after 4 years of therapy (n=32). Conclusions: A large pool of HIV-infected cells is rapidly established in vertically infected Thai infants. Early ART initiation (within 3 months of life) is associated with a rapid initial decay of all HIV reservoir markers, followed by a stable second-phase. The proportion of children with detectable inducible reservoir as measured by TILDA continues to decrease after 3 years on ART, suggesting that prolonged therapy may have long-term benefits in this population.

Poster Abstracts

CROI 2025 329