CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

and the development of antiviral immunity between childhood, adolescence and young adulthood in terms of a) expression of co-inhibitory receptors; and b) expression of plasma cytokines. Methods: Expression of co-inhibitory receptors was measured by flow cytometry. Levels of 33 plasma cytokines and chemokines were assessed using the Meso Scale Discovery platform. Total HIV DNA was measured by qRT-PCR and inducible HIV RNA levels were measured following prostratin stimulation. HIV specific cell-mediated immune responses were measured using IFN-g ELISPOT. Results: The study was conducted on 65 participants of the EPIC4 Cohort (47.4% male) who were stratified as children (<10 yrs; n=15), adolescents (10-18 yrs; n=34) or young adults (>18; n=16). Median viral load was <40 RNA copies/ mL plasma (range=<40-8473 copies). Frequencies of CD4+ T cells expressing PD-1 or TIGIT and of CD8+ T cells expressing PD-1, TIGIT or CD160 significantly increased with age. Total HIV DNA and inducible HIV RNA levels were positively correlated with frequencies of PD-1+ (p≤0.033) and TIGIT+ (p≤0.032) CD4+ T cells and of PD-1+ (p<0.001), TIGIT+ (p≤0.080) and CD160+ (p≤0.021) CD8+ T cells (Figure). Children clustered separately from adolescents and young adults in PCA whether reservoir size or HIV-specific cell-mediated immune responses were included. Unbiased PCA showed that global variability in the plasma cytokine profile on the first PC (27.4% variability) was significantly (p<0.05) associated with age at sample collection, while the second PC (15.04% variability) was linked to HIV reservoir size. Plasma levels of TGF-b and TH2 cytokines (e.g., IL-4) were significantly elevated in children <10. A subset of older participants (>10 years) with high TGF-b levels did not exhibit high levels of inducible HIV RNA. Conversely, older participants with reduced levels of TGF-b showed higher levels of IL-17A, IFN-g, total HIV DNA and inducible HIV RNA. Conclusions: Expression of a set of co-inhibitory receptors (PD-1, TIGIT, CD160) and evolution of cytokine profiles were associated with age and with total and inducible HIV reservoir size in children and adolescents living with vertically acquired HIV. This study highlights major longitudinal shifts in mobilization of immune pathways that could inform the differential pathology of pediatric HIV disease.

planned or unplanned ART interruptions could also enroll if ART had been resumed for >2 years after interruption. HIV-1 DNA was measured in PBMCs using droplet-digital PCR. Associations between DNA levels and preceding factors were investigated with descriptive statistics and chi-square tests. Results: ART was started at a median of 65 days (IQR 52-85) among 87 participants (49.4% male) enrolled in this study at a median of 13.2 years of age (IQR 9.6-16.7). Overall, the median HIV-1 DNA level was 340 copies/10 6 cells (IQR: 145- 909) and 10.3% were below the threshold of detection (<1 copy/10 6 cells). Distributions of HIV-1 DNA did not differ between male and female participants; and, within this truncated range of age of ART start, those starting ART <60 days of age had HIV-1 DNA median 240 copies/10 6 cells (IQR 83-873; 12.8% undetectable) similar to those starting >60 days: median 396 copies/10 6 cells (IQR 208-943, 8.3% undetectable). Undetectable HIV-1 DNA was more frequent in those who had undergone a past ART interruption (22.7%) than those who had remained on continuous ART (6.3%) p=0.04. Median age of ART interruption was 1.4 years, two-thirds were planned interruptions as part of the CHER study, and the median duration of interruption was 2.4 months. There were no differences in age of ART start or sex distribution between those with and without a history of interruption. Conclusions: Around 10% of early-treated children and adolescents well suppressed on ART for more than a decade had HIV-1 DNA levels below the assay’s detection threshold. Having undergone a prior ART interruption was associated with greater likelihood of undetectable HIV-1 DNA. These results provide intriguing support for the concept of “auto-immunization,” where ART interruption is undertaken to bolster HIV immunity toward ART-free viral control.

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Poster Abstracts

1033 Proviral HIV-1 DNA Below Detection in Early Treated Adolescents After Prior Treatment Interruption Louise Kuhn 1 , Kavidha Reddy 2 , Chantal Molechan 3 , Kennedy Otwombe 4 , Ana Barrios 1 , Shaun Barnabas 5 , Thanyawee Puthanakit 6 , Diana Rutebarika 7 , Tacilta Nhampossa 8 , Maria G. Lain 9 , Almoustapha Maiga 10 , Moira Spyer 11 , Paolo Palma 12 , Mathias Lichterfeld 13 , Mark Cotton 5 , for the CARMA-Global Study Team of the EPIICAL Consortium 1 Columbia University Irving Medical Center, New York, NY, USA, 2 Africa Health Research Institute, Mtubatuba, South Africa, 3 University of KwaZulu-Natal, Durban, South Africa, 4 Perinatal HIV Research Unit, Soweto, South Africa, 5 Family Clinical Research Unit, Tygerberg, South Africa, 6 Chulalongkorn Hospital, Bangkok, Thailand, 7 Joint Clinical Research Centre, Kampala, Uganda, 8 Manhiça International Research Center, Manhiça, Mozambique, 9 Fundação Ariel Glaser Contra o SIDA Pediátrico, Maputo, Mozambique, 10 Centre Hospitalier Universitaire du Point G, Bamako, Mali, 11 UCL Great Ormond Street Institute of Child Health, London, UK, 12 Bambino Gesu Children's Hospital, Rome, Italy, 13 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA Background: Undetectable or low HIV-1 DNA levels have been associated with a greater likelihood of ART-free viral control in adults treated during primary infection. Here we investigate predictors of HIV-1 DNA levels in a cohort of early treated children and adolescents recruited on characteristics expected to make them good candidates for future remission/cure trials. Methods: Parents or guardians of children and adolescents with perinatally acquired HIV starting ART <3 months of age, >7 years prior and with plasma HIV-1 RNA <50 copies/ml on ART were recruited at 8 sites in South Africa, Mozambique, Uganda, Mali and Thailand. Children who had undergone prior

1034 Pediatric ART Interruptions Transiently Raise HIV DNA Without Large Changes to Long-Term Reservoirs Daniel B. Reeves 1 , Morgan Litchford 1 , Carolyn Fish 1 , Noah Cassidy 1 , Agnes Langat 2 , Daisy Chebet 2 , Helen Moraa 2 , Jennifer Slyker 3 , Sarah Benki 3 , Julie Overbaugh 1 , Dalton Wamalwa 2 , Grace John-Stewart 3 , Joshua T. Schiffer 1 , Dara A. Lehman 1 1 Fred Hutchinson Cancer Center, Seattle, WA, USA, 2 University of Nairobi, Nairobi, Kenya, 3 University of Washington, Seattle, WA, USA Background: To inform pediatric HIV persistence inclusive of scenarios where antiretroviral therapy (ART) usage may not be completely suppressive, we sought to elucidate reservoir dynamics with and without occasional HIV RNA viremia. Methods: In Kenyan children living with HIV who initiated ART between 1-12 months of age (median 3 months), we measured HIV RNA and HIV DNA (3-probe-classified intact vs. defective via our cross-subtype intact proviral DNA assay “CS-IPDA”) for up to 8 years of follow up. HIV RNA was quantified every 3-6 months resulting in median of 19 (range 1-32) HIV RNA observations. DNA was quantified approximately every 6 months during the first two years of ART and then every 2 years afterwards resulting in a median of 5 (range 1-10) HIV DNA measurements per child. We developed mathematical models to integrate HIV RNA and DNA data and estimate reservoir decay rates from 57 children who

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