CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

Results: Group A included 561 participants at 41 sites in 10 countries and Group B 74 participants at 13 sites in 3 countries. 95% of Group A and 100% of Group B completed study follow-up to Wk72. Group A: At end of study, 86.1% of 2-CpG (n=173), 97.2% of 3-CpG (n=177), and 57.5% of 3-alum (n=174) had SPR. SPR% difference was 28.6% (18.0%,38.4%) for 2-CPG v. 3-alum, 39.2% (30.0%,47.9%) for 3-CpG v. 3-alum, and 11.0% (4.3%,18.1%) for 3-CpG v. 2-CpG. The proportion who achieved SPR at any time on study but had anti-HBs <10 mIU/mL by study end was 2.1% for 3-CpG, 10.7% for 2-CpG and 22.0% in 3-alum. Among those with anti-HBs >1000 mIU/mL at the primary vaccine response time (Wk28 for 3-dose arms and Wk12 for 2-dose), 100% in all arms had SPR at study end. Overall, 73.3% (66.5%,79.1%), 77.7% (71.2%,83.0%), and 73.7% (66.9%,79.5%) of participants in 2-CpG, 3-CpG, and 3-alum reported AEs; two deaths unrelated to vaccines (TB, Wk43 2-CpG; and cardiac arrest, Wk36 3-CpG). Group B: At the end of study, 97.3% (90.7%,99.3%) of 74 participants had SPR. The 2 participants with anti-HBs <10 mIU/mL were among those with the lowest anti-HBs titers at time of primary vaccine response time. 87.8% (78.5%, 93.5%) reported AEs; no deaths. Conclusions: In PWH, higher end of study seroprotection was achieved with HepB-CpG over HepB-alum, and 3 doses of HepB-CpG over 2 doses. HepB-CpG achieved durable seroprotection in both vaccine-naïve and prior vaccine non response groups.

between relative percent (%) change in IHTG (PCHG) and DNAm indicators, controlling for sex at birth and age. Results: At entry, the mean age of participants (n=41) was 49 years (39% female), CD4+ T cell count was 776 cells/mm 3 and absolute IHTG was 12.7%. Relative IHTG decrease was -29% (95% CI: -37, -20). The mean epigenetic age estimate at entry for DNAmFitAge was 59.2 years (mean epigenetic age acceleration of 10.2 years). A less accelerated DNAmFitAge at entry was associated with greater IHTG improvements (β=-1.6, p=0.10) when controlling for sex and chronological age. Weaker DNAmGripmax was also associated with greater improvements in IHTG over 24 weeks (β=4.68, p=0.009) when controlling for sex and chronological age. Conclusions: Epigenetic age indicators incorporating physical fitness, specifically worse DNAmGripmax and younger DNAmFitAge were associated with greater improvements in IHTG following 24 weeks of low-dose semaglutide treatment in PWH, suggesting a potential role for epigenetic biomarkers in predicting treatment responses.

Oral Abstracts

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Supplemental High-Dose Rifampicin and Levofloxacin for Inpatients With Disseminated HIV-TB Graeme Meintjes 1 , Phiona Namale 1 , David Barr 2 , Linda Boloko 1 , Marcia C. Vermeulen 1 , Bryony Simmons 3 , Andrew Hill 4 , Sean Wasserman 5 , Kate Haigh 4 , Freedom Gumedze 1 , Ayanda T. Mnguni 1 , Thomas Crede 1 , Yakoob Vallie 1 , Gary Maartens 1 , Charlotte Schutz 1 , for the New Strat-TB Study Group 1 University of Cape Town, Cape Town, South Africa, 2 Queen Elizabeth University Hospital, Glasgow, UK, 3 London School of Economics, London, UK, 4 University of Liverpool, Liverpool, UK, 5 St George's University of London, London, UK Background: Disseminated TB is a common cause of hospitalisation for people with HIV and has high early mortality. Methods: The NEW STRAT-TB trial, conducted at 3 hospitals in Cape Town, South Africa, has a 2x2 factorial randomization to standard TB treatment versus intensified TB treatment (standard TB treatment with rifampicin dose increased to 35mg/kg/d plus levofloxacin) and prednisone (1.5mg/kg/d) versus identical placebo, for the initial 14 days, followed by standard TB treatment. Adults admitted to hospital with HIV-associated disseminated TB (one or more of urine Alere LAM, urine Xpert Ultra or blood Xpert Ultra positive) are eligible. The primary endpoint is 12-week mortality. The absolute difference between arms was estimated using the Kaplan-Meier method with bootstrapping to obtain 95% confidence intervals and associated p-values. Results: On 6 June 2024, the intensified TB treatment arm was stopped by the DSMB due to higher 2-week mortality. Investigators remain blinded to prednisone versus placebo allocation. 580 participants (of planned 732) had been enrolled with 563 in mITT population. Median age was 36 years (interquartile range, IQR=30-43), 299 (53%) were female with median CD4 count 42 cells/μL (IQR=18-92), Hb 8.2 g/dL (IQR=6.9-9.6), venous lactate 2.1 mmol/L (IQR=1.6 2.9) and creatinine 70μmol/L (IQR=52-102). 113 (20%) had eGFR < 50mL/min. 83%, 67% and 31% were positive by urine Xpert Ultra, urine Alere LAM and blood Xpert Ultra, respectively. 55/548 participants (10%) had HIV RNA < 50 copies/mL. 14-day mortality was 31/283 (11.0%) in the intensified arm and 14/280 (5.0%) in the standard arm (difference 6.0%; 95%CI 1.6% - 10.4%; p=0.008). Mortality at 12 weeks was 55/283 (19.4%) in the intensified arm and 43/280 (15.4%) in

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Epigenetic Age Predictors of Semaglutide-Related Liver Fat Changes in People With HIV Michael J. Corley 1 , Alina Pang 1 , Doug Kitch 2 , Amy Kantor 2 , Fred R. Sattler 3 , Pablo Belaunzarán-Zamudio 4 , Todd Brown 5 , Alan Landay 6 , Kristine M. Erlandson 7 , Jordan Lake 8 1 Weill Cornell Medicine, New York, NY, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of Southern California, Los Angeles, CA, USA, 4 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 5 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 6 University of Texas Medical Branch, Galveston, TX, USA, 7 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 8 University of Texas Health Science Center at Houston, Houston, TX, USA Background: In a recent pilot study (ACTG A5371, SLIM LIVER: NCT04216589), 24 weeks of low-dose semaglutide (1 mg sc weekly) reduced metabolic dysfunction associated steatotic liver disease (MASLD) in people with HIV (PWH), with 58% having improved MRI-proton-derived fat fraction-quantified intrahepatic triglycerides (IHTG). Although trends suggested greater IHTG improvements in women and older participants, the role of biological age indicators was not assessed. We investigated whether epigenetic indicators incorporating physical fitness were associated with IHTG changes on semaglutide. Methods: The SLIM LIVER study enrolled PWH ≥18 years on suppressive ART with central adiposity and MASLD. All participants received semaglutide for 24 weeks and PBMCs were available at weeks 0 and 24. Genome-wide DNA methylation profiles were analyzed in 41 participants with available PBMCs and used to calculate DNAm-based aging biomarkers, DNAmFitAge, that provides an estimate of biological age using DNAm-based estimates of three physical fitness measurements: maximal oxygen uptake (DNAmVO2max), maximal gripping force (DNAmGripmax), and gait speed (DNAmGaitspeed). R code was used calculate DNAm fitness biomarkers available at GitHub repository at https://github.com/ kristenmcgreevy/DNAmFitAge. Linear regression models evaluated relationships

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CROI 2025