CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

898

Incident Diabetes Among People With HIV After Switching to Integrase Strand Transfer Inhibitors Y. Joseph Hwang 1 , Catherine Lesko 2 , Todd Brown 1 , G. Caleb Alexander 1 , Lauren Zalla 2 , Jarratt Pytell 3 , Seun Falade 4 , Richard Moore 2 , Keri N. Althoff 2 , Jonathan Colasanti 5 , M. John Gill 6 , Vincent C. Marconi 5 , Michael Horberg 7 , Maile Karris 8 , Anthony Todd Fojo 1 , for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 3 University of Colorado School of Medicine, Aurora, CO, USA, 4 The Johns Hopkins Hospital, Baltimore, MD, USA, 5 Emory University, Atlanta, GA, USA, 6 University of Calgary, Calgary, Canada, 7 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA, 8 University of California San Diego Medical Center, La Jolla, CA, USA Background: Initiation of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is associated with weight gain and diabetes mellitus (DM) among ART-naïve people with HIV (PWH). However, most are ART-experienced and may switch to an INSTI-based ART from a different antiretroviral regimen. We aimed to estimate the risk of incident DM associated with switching from a non-nucleoside reverse-transcriptase inhibitor (NNRTI) or protease inhibitor (PI) to an INSTI in a large, diverse cohort of ART-experienced PWH. Methods: We studied PWH aged ≥18 years in the North American AIDS Cohort Collaboration on Research and Design who did not have DM history and had used NNRTI or PI for ≥180 days between 2007 and 2021. Our study design emulated a trial with multiple baselines: at each HIV clinic visit, participants were eligible to either continue NNRTI or PI or switch to INSTI (bictegravir, dolutegravir, elvitegravir, or raltegravir). We followed participants from each eligible index visits until incident DM, death, loss to follow-up, or administrative censoring at the end of study period or 10 years follow-up. We used inverse probability of treatment weights to balance treatment groups on demographics, body mass index, viral suppression status, comorbidities, and comedications (including tenofovir formulations). We additionally censored follow-up time if people switched to INSTI after the index visit and used weights to mitigate potential bias from informative censoring. We estimated hazard ratios (HRs) using weighted Cox regression with robust variance estimator. Results: We included 58,971 PWH who attended 727,053 visits where they continued NNRTI or PI and 12,976 visits where they switched to INSTI. The median age was 51 years and 86% were male at birth. Switching to an INSTI was associated with a higher risk of incident DM (weighted HR, 1.53; 95% confidence intervals [CI], 1.27–1.85) compared to continuing an NNRTI or PI. Switching to specific INSTIs also conferred increased DM risk (weighted HRs 1.47–1.91; Table). In a post-hoc analysis of index clinic visits from 2016 onwards, switching to an INSTI was associated with weighted HR of 1.19 (95% CI, 0.92–1.54). Conclusions: Switching from an NNRTI or PI to an INSTI was associated with an increased risk of incident DM in this diverse cohort of PWH from multiple sites across North America. These findings inform antiretroviral prescribing and tailored risk-benefit approach for PWH, especially those with clinical concern for new-onset DM.

897

Body Composition Changes in People With HIV Switching to DTG/3TC or BIC/TAF/FTC Silvana Di Gregorio 1 , Lucas R. Brun 2 , Santiago Mourelo 3 , Mar Masiá 4 , Lucio Jesús Garcia Fraile Fraile 5 , Maria J. Crusells 6 , Pere Domingo 7 , Adrian Curran 8 , Roberto Güerri 9 , Pablo Ryan 10 , Jose L. Blanco 11 , Maria-Jesus Vazquez 12 , Marta De Miguel 13 , Belen Alejos 14 , Esteban Martinez 11 , for the PASO-DOBLE (GeSIDA 11720) Randomized Trial Team 1 CreuBlanca, Barcelona, Spain, 2 Universidad Nacional de Rosario, Rosario, Argentina, 3 ASCIRES CETIR, Barcelona, Spain, 4 Hospital General Universitario de Elche, Elche, Spain, 5 Hospital Universitario de La Princesa, Madrid, Spain, 6 Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, 7 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 8 Hospital Universitari Vall d'Hebron, Barcelona, Spain, 9 Hospital del Mar, Barcelona, Spain, 10 Hospital Universitario Infanta Leonor, Madrid, Spain, 11 Hospital Clinic of Barcelona, Barcelona, Spain, 12 ViiV Healthcare, Madrid, Spain, 13 Fundación SEIMC-GeSIDA, Madrid, Spain, 14 Independent Consultant, Madrid, Spain Background: Switching to DTG/3TC (DOV) or BIC/FTC/TAF (BIK) in the PASO DOBLE trial (ClinicalTrials.gov NCT04884139) showed noninferior efficacy of DOV vs. BIK and weight gain in both groups, which was significantly greater for BIK at 48 weeks. We aimed to know how switching to DOV or BIK affects body composition and whether there are differences between the two regimens. Methods: Participants in the PASO-DOBLE trial underwent whole-body DXA scans to assess total mass (TM), fat mass [total (FM) and regional, including abdominal (ABFM), visceral (VFM), and appendicular (LFM)], and lean mass [total (LM), and appendicular (ALM)] and a single abdominal CT scan at L4 level to measure subcutaneous (SAT), visceral (VAT), and total (TAT) fat area at baseline and 48 weeks. Mean changes in the pooled population were used to estimate the impact of switching to DOV or BIK on body composition. Linear regression adjusted by sex, TAF at baseline, age and race was used to assess differences in compartments between DOV or BIK. DXA-defined obesity (FM >25% men; >32% women) was assessed at baseline and 48 weeks. Results: Out of 553 participants in the trial, 447 (81%) (DOV, n=223; BIK, n=224) had paired DXA and CT scans available and were analyzed. At baseline, mean (IQR) age was 50 (40-57) years, 27% were women, 35% on TDF, and 26% on EFV. In the pooled population, there were significant mean (95% CI) increases in DXA-derived TM +1.2% (0.7, 1.7), FM +17.9% (14.6, 21.2), ABFM +23.9% (18.6, 29.2), VFM +82.4% (29.7, 135.3), LFM +21.7% (17.9, 25.5); decreases in DXA-derived LM -2.6% (-3.2, -2.0), and ALM -2.8% (-3.6, -2.1); and increases in CT-derived VAT +21.2% (14.5, 27.8) and TAT +1.5% (0.0, 2.9), but no changes in SAT 0.0% (-1.4, 1.4). Adjusted mean treatment differences (95% CI) BIK minus DOV in changes from baseline are shown in the table; in general, total and fat mass increased more and lean mass decreased less with BIK vs. DOV. DXA-defined obesity increased from baseline (DOV 57.7%, BIK 57.0%) to 48 weeks (DOV 71.3%, BIK 73.5%) [adjusted OR (95% CI) for treatment difference 1.31 (0.76; 2.23)] in both arms. Changes in all fat compartments were positively correlated with changes in insulin resistance (p<0.04). Conclusions: Switching to DOV or BIK was associated with fat gain, which was relatively greater at the visceral compartment, and lean mass loss. Increases in TM and LFM were significantly greater with BIK than with DOV. Fat gain in any compartment was associated with insulin resistance.

Poster Abstracts

899

Decreased Adipose Tissue Gene Expression After a 48-Week Switch From an InSTI Regimen to TDF/3TC/DOR Christine Katlama 1 , Antoine Faycal 1 , Kenza Ngono-Ayssi 2 , Luminita Schneider 1 , Marc-Antoine Valantin 1 , Claudine Duvivier 3 , Zineb Ouazene 4 , Christia Palacios 5 , Aissata Didine Kaba 2 , Yasmine Dudoit 2 , Claire Lagathu 2 , Veronique Béréziat 2 , Lambert Assoumou 1 , Jacqueline Capeau 2 , Jennifer Gorwood 2 , for the ADDORE Study Group 1 Assistance Publique – Hôpitaux de Paris, Paris, France, 2 Sorbonne University, Paris, France, 3 Necker Hospital, Paris, France, 4 Hospital Saint-Antoine, Paris, France, 5 Tenon Hospital, Paris, France Background: INSTIs are known to induce weight/fat gain, the pathogenesis and reversibility of which remain unclear. The ongoing ADDORE study aimed to

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