CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: HIV-1 reservoirs in perinatal infections are susceptible to reactivation with TLR7 agonists and HDAC inhibitors through upregulation of pro-inflammatory pathways mediated by IFNs, TGF- β, TNFα and IL-2, offering insights into proviral reactivation and control for AdLWPH. The figure, table, or graphic for this abstract has been removed. 1044 Maternal Antiretroviral Formulation Preferences for Neonates Charlene Purdy 1 , Lario Viljoen 1 , Verah N. Luke 1 , Samantha du Toit 1 , Maria Groenewald 1 , Lindee Ganger 1 , Anneke C. Hesseling 1 , Anthony Garcia-Prats 2 , Tim Cressey 3 , Adrie Bekker 1 1 Stellenbosch University, Cape Town, South Africa, 2 University of Wisconsin–Madison, Madison, WI, USA, 3 Chiang Mai University, Chiang Mai, Thailand Background: Oral liquids and syrup formulations of zidovudine (ZDV) and nevirapine (NVP) are the cornerstone of antiretrovirals (ARVs) for neonates born to mothers with HIV for prevention and treatment. These formulations have a short shelf-life, poor palatability, require frequent dosing, and are associated with stock-outs. The World Health Organization recommends switching to solid oral dosage forms soonest, with ARV dispersible tablets preferred over syrups for children. We assessed preferences for ARV formulations among mothers with neonates enrolled in the PETITE-DTG study. Methods: PETITE-DTG is an ongoing phase I/II, open-label, two-stage study conducted in South Africa (NCT05590325) evaluating the pharmacokinetics, safety and acceptability of 2 solid pediatric dolutegravir (DTG) formulations in neonates. Neonates were randomized to receive either a 5mg DTG dispersible tablet (DTG-DT) or a 5mg novel DTG oral dispersible film (DTG-OF), with ZDV prophylaxis. Interviews were conducted in a sub-set of mothers (n=26) to determine infant ARV formulation preferences. Assessments included relative ranking of formulation preferences of 3 existing (DTG-DT, ZDV, NVP), 1 novel (DTG-OF), and 2 formulations in development (long-acting injectable, transdermal patch). We characterized and compared preferences using rank summaries (1 = most preferred; 6 = least preferred). Results: Mothers had a strong preference for DTG-OF (score 56), independent of the DTG formulation their infants received (Table 1). Reported advantages included ease of administration, confidence in full dose administration, and perceived discreetness. Next was the long-acting injectable (score 66), reported as familiar, positively compared to routine vaccines, and, despite feared discomfort for babies, described as convenient (monthly vs daily). DTG-DT (score 96) was described as palatable for babies but caregivers were worried about preparation and dosing volume. For existing syrups (ZDV, NVP; score 99, 104) mothers cited concerns with administration frequency and underdosing (spillage, spitting). The transdermal patches ranked the lowest (score 125) with mothers fearing interaction with water, discomfort for infants, and uncertainties regarding effectiveness. Conclusions: Mothers preferred the use of solid oral ARVs above syrups, with a strong preference for the DTG-OF even if their babies were receiving DTG-DT. Monthly injectables were also preferred, highlighting the importance of usability, ease of administration, and dosing frequency.

and effector functions of HIV-specific CD8+ T cells in longitudinal blood specimens from PWH who began ART during acute or chronic infection and from ECs. Methods: PBMC collected prior to ART and up to 4 timepoints after ART initiation were obtained from the UCSF SCOPE cohort (n = 16 acute, n = 10 chronic, n = 10 ECs). Cells were analyzed using a 40-parameter CyTOF panel at baseline and following a 6-hour stimulation with peptides spanning the HIV proteins Gag, Pol, Env, Tat, and Nef. HIV-specific T cells were assessed using a combination of 9 effector cytokines/chemokines and 3 cytolytic/degranulation markers. Results: In all cohorts, most HIV-specific T cells induced IFNg, TNFa, and the degranulation marker CD107a. Prior to ART, HIV-specific CD8+ T cell frequencies were higher in the chronic-treated and EC cohorts compared to the acute treated cohort. Pre-ART, expression of CTLA-4, a marker of cellular exhaustion, was elevated on HIV-specific CD8+ T cells from the chronic-treated and EC groups relative to the acute-treated group (p<0.004). However, expression of the follicle-homing receptor CXCR5 was uniquely elevated on HIV-specific CD8+ T cells from ECs compared to the other groups (p<0.0005). After ART, HIV-specific CD8+ T cell frequencies declined in ECs (p<0.005) but remained unchanged in the acute and chronic-treated groups. Conclusions: Our data suggest that the frequencies of HIV-specific CD8+ T cells are decreased by ART in ECs, but not in acute or chronic-treated PWH. HIV specific CD8+ cells from ECs, like those from chronic-treated PWH, expressed the exhaustion marker CTLA4, possibly due to chronic antigen stimulation. However, HIV-specific CD8+ T cells from ECs uniquely express high levels of CXCR5, which may help direct these effector cells to lymphoid follicles, a primary site of HIV persistence. Our findings suggest that HIV-specific CD8+ T cells in ECs have distinguishing phenotypic features that may explain their ability to mediate ART-free HIV control. 1043 Transcriptomics of Proviral Latency Reversal in Reservoirs of Youth With Perinatal HIV-1 Kristen Kelly 1 , Adit Dhummakupt 2 , Kedi Le 1 , Weiqiang Zhou 1 , Hongkai Ji 1 , Joseph Szewczyk 2 , Ya Hui Chen 2 , Elise Ohene-Kyei 2 , Thuy Anderson 2 , Allison Agwu 2 , Deborah Persaud 2 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Latency reversing agents (LRAs) such as TLR agonists and histone deacetylase (HDAC) inhibitors reactivate HIV-1 from latency in adults. We examined the immune effects of the TLR7 agonist GS-9620, alone and in combination with the HDAC inhibitor SAHA, in ex-vivo studies of adolescents with perinatal HIV-1 (AdLWPH), aiming to inform latency reversal strategies for this population. Methods: Enriched CD4 T cells from 16 AdLWPH (median age 17.8[IQR, 13.8-20.1] yrs; median virologic suppression of 10.4[6-16.2] yrs; 81.3% female) were stimulated with GS-9620, SAHA, or in combination. PHA/PMA/Ionomycin (PPI) and vehicle control (VC) were studied in parallel. HIV-1 reservoir size was measured by the intact proviral DNA assay. Proviral transcription was assessed by induction of multiply spliced (ms) tat/rev HIV-1 RNA transcripts (msRUPM) with the Tat/Rev Limiting Dilution Assay (TILDA). LRA immune effects were analyzed by flow cytometry for immune activation markers. Transcriptomic effects were examined by bulk RNA-seq in 7 participants (71.4% female) for all treatment groups. Participants were categorized as high or low responders based on fold change of msRUPM (>1.1); differential gene expression analyses were applied. Results: The median intact HIV-1 DNA load was 15.8[4.7-50.0] copies/10 6 CD4 T cells. With VC, ms-HIV-1 RNA transcripts were detected in 12/16 participants (range 1-22.3). PPI, GS-9620, and GS-9620+SAHA increased ms-HIV-1 RNA relative to VC by 2.0-,1.4- and 1.6-fold. The proportion of intact proviruses induced was significantly increased relative to VC with PPI and GS-9620. PPI was associated with upregulation of activation markers CD69, CD25, and HLA DR, whereas GS-9620, SAHA or the combination were only associated with CD69 upregulation. Across all treatment conditions, IFNγ response was associated with high msRUPM. Without LRA stimulation, IFNγ and IFNα upregulation was associated with high basal msRUPM. IFNγ response was also associated with high msRUPM across all conditions. High GS-9620 responders had upregulation of IFNα, TNFα and IL-2, while high SAHA responders had upregulated TGF-β. High GS-9620+SAHA responders had upregulated TNFα, interferon and estrogen responses (Table 1).

Poster Abstracts

CROI 2025 334