CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

suppressed viremia as well as in an additional 65 children who did not fully suppress and/or experienced ART interruptions with HIV RNA viremia above 1000 copies/mL. Results: Our model linked periods of HIV RNA viremia to transient rises in both intact and defective HIV DNA. However, after HIV RNA resuppression, HIV DNA levels and decay rates returned to pre-viremic levels ( Fig ). Consistent with this, long term intact and defective HIV DNA decay rates were not different in CWH with and without treatment interruptions. Estimates (mean and [95% confidence interval]) for HIV DNA decay from CWH who suppressed HIV RNA below 1000 copies/mL by 6 months of ART were biphasic for year 0-1 and 1-8 of ART – intact HIV DNA: 2.7 [2–4.1] followed by 22 [10.5–∞] month half-life; defective HIV DNA: 8.6 [5.4–20.7] month half-life followed by 101 [54–845] month doubling time. We found that there was a moderate relationship between the number of months in which CWH had observed HIV RNA above 1000 copies/mL during follow-up and the HIV DNA level at study end, 8 years after ART initiation (Spearman rho=0.6, p=0.004 and rho=0.5, p=0.01 for intact and defective HIV DNA, respectively). Conclusions: Models show viremia correlate with rises in HIV DNA, but rises were transient, suggesting most HIV DNA created during treatment interruptions is short lived. Our results also raise the possibility that in CWH, primary infection more effectively seeds long term reservoirs than treatment interruptions after ART is initiated.

3, EFV-based, and LPV/r-based in 1 each. Integrated HIV DNA ranged from 11-87 copies/10 6 CD4 T cells, all had undetectable inducible virus by TILDA assay. Two of the 5 participants had HIV antibodies to Gag and Pol and none had antibodies to Env. All children had detectable (IFN-γ+) Env-specific CD4+ T cell responses whereas Env-specific CD8+ T cells responses were detected in 2/5 participants. Gag-specific CD4+ and CD8+ T cell responses were detected in 2 and 1 children respectively. Pol-specific T cell responses were absent. Conclusions: Some children who received very early ART had low HIV reservoirs and are potential candidates for ATI. However, they had limited HIV-specific CD4+ and CD8+ T cell response. Research strategy for ART-free virological control should consider boosting HIV-specific immunity prior to ATI.

Poster Abstracts

1036 Association Between HIV-Specific Antibodies and HIV Reservoir Markers in Early Treated Children Rapisa Nantanee 1 , Suvaporn Anugulruengkitt 1 , Wipaporn Natalie Songtaweesin 1 , Siriwat Akapirat 2 , Supranee Buranapraditkun 1 , Amélie Pagliuzza 3 , Marta Massanella 4 , Jinnaphak Seesuksai 1 , Monta Tawan 1 , Thidarat Jupimai 1 , Sasiwimol Ubolyam 5 , Julie Mitchell 6 , Nicolas Chomont 7 , Lydie Trautmann 8 , Thanyawee Puthanakit 9 , for the HIVNAT209 Study Group 1 Chulalongkorn University, Bangkok, Thailand, 2 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 3 Centre de Recherche du CHUM, Montreal, Canada, 4 IrsiCaixa, Badalona, Spain, 5 Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 6 Oregon Health and Science University, Portland, OR, USA, 7 Université de Montréal, Montreal, Canada, 8 Henry M Jackson Foundation, Bethesda, MD, USA, 9 Chulalongkorn Hospital, Bangkok, Thailand Background: Children who initiated early antiretroviral therapy (ART) are potential candidates for ART-free virological control. Low antibody responses to Env (gp160, gp41) or Gag (p24) HIV proteins have been reported associated with low HIV reservoir size. This study aimed to characterize HIV protein-specific antibody and HIV reservoir size in children who initiated early ART and had sustained virological suppression. Methods: Children aged 6-10 years who initiated ART within 6 months of age and sustained virological suppression were enrolled. HIV antibodies were detected by western blot assay (WB) to 10 proteins: Env (gp160, gp120, gp41), Pol (p65, p51, p31), and Gag (p55, p40, p24, p18) and chemiluminescent microparticle immunoassay (CMIA). HIV reservoir size was measured by tat/rev induced limiting dilution assay (TILDA) and integrated HIV DNA. Results: Between March and April 2024, 23 children were enrolled. ART was initiated at the median (interquartile range, IQR) age of 73 (45-99) days, and 17 (74%) initiated ART within 3 months of age. The median (IQR) age was 8.4 (7.0-9.5) years, CD4+ T cells was 814 (670-1191) cells/mm 3 , and integrated HIV DNA was 47 (15-87) copies/10 6 CD4+ T cells. WBs were positive for Env in 3 (13%), Pol in 10 (44%), and Gag in 14 (61%) children. Children who had negative HIV antibody by CMIA (n=14) had no response to Env-gp160 protein (0% vs 33%, p=0.04), low response to Env-gp41 protein (0% vs 11%, p=0.39) and significantly lower response to Gag-p24 (43% vs 89%, p=0.04), as shown in Figure 1A. There was no statistically significant difference in HIV-specific antibody responses between the 11 (61%) children who had undetectable HIV reservoir by TILDA assay and the 7 (39%) children with detectable TILDA (Figure 1B). There was no statistically significant difference in HIV-specific antibody responses among children with integrated HIV DNA > or ≤ 50 copies/10 6 CD4+ T cells (p>0.05). Conclusions: Children with early ART had low HIV-specific antibodies to Env. No strong association between HIV-specific antibody response by WB and HIV reservoir by TILDA or integrated HIV DNA levels was found. Identification of

1035 Children With Very Early ART and Favorable Profiles for ART-Free Viral Control Research: Thai Cohort Rapisa Nantanee 1 , Suvaporn Anugulruengkitt 1 , Wipaporn Natalie Songtaweesin 1 , Supranee Buranapraditkun 1 , Amélie Pagliuzza 2 , Marta Massanella 3 , Jinnaphak Seesuksai 1 , Monta Tawan 1 , Thidarat Jupimai 1 , Siriwat Akapirat 4 , Sasiwimol Ubolyam 5 , Julie Mitchell 6 , Nicolas Chomont 7 , Lydie Trautmann 8 , Thanyawee Puthanakit 9 , for the HIVNAT209 Study Group 1 Chulalongkorn University, Bangkok, Thailand, 2 Centre de Recherche du CHUM, Montreal, Canada, 3 IrsiCaixa, Badalona, Spain, 4 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 5 Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 6 Oregon Health and Science University, Portland, OR, USA, 7 Université de Montréal, Montreal, Canada, 8 Henry M Jackson Foundation, Bethesda, MD, USA, 9 Chulalongkorn Hospital, Bangkok, Thailand Background: Data from IMPAACT P1115 showed proof of concept that children who received very early antiretroviral therapy (ART) and displayed restricted HIV viral reservoirs could achieve >48 weeks of virological control upon analytical treatment interruption (ATI). In this study, we characterized Thai children who received very early ART and had favorable profiles for ART-free virological control. Methods: We performed a follow-up study of 24 neonates who were born between 2015-2018 and received ART within 24 hours of life. Participants who received neonatal prophylaxis and transitioned to treatment dosage were included. The following criteria were used to define “favorable profiles” for enrollment eligibility: (1) sustained viral suppression (HIV RNA <200 copies/mL) (2) negative HIV antibodies by chemiluminescent microparticle immunoassay (3) low integrated HIV DNA < 2 log 10 per million CD4+ T cells (4) undetectable inducible HIV virus by tat/rev induced limiting dilution assay (TILDA). We measured HIV antibodies by Western blot and HIV-specific CD4+ and CD8+ T cell responses by multiparameter flow cytometry with activation-induced marker and intracellular cytokine staining after stimulation with Gag, Pol and Env peptides. Results: Thirteen participants were ineligible because of virological failure/ poor adherence (n=11) or the presence of detectable HIV antibodies (n=2). Between March and April 2024, 5 out of 11 eligible participants were enrolled (Table 1). Current median (IQR) age was 7 (7.0-7.5) years and 80% were male. Three children acquired HIV in-utero. Current ART regimens were DTG-based in

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