CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusions: After two years, the expression of different sets of inflammatory proteins significantly decreased in both ART groups. These molecules are involved in relevant functions related to inflammation. The higher baseline inflammation in the BIC/F/TAF group, which resolved after two years, suggests that factors associated with greater inflammation may influence regimen selection and that this therapy effectively neutralized the initial disparity. Effectiveness and Inflammatory Markers After 144 Weeks of Switch to DTG/3TC in a Randomized Trial Evy Blomme 1 , Evelien De Smet 1 , Elianne Burg 1 , Loïc Schrooyen 1 , Sophie Degroote 2 , Sophie Vanherrewege 2 , Els Caluwe 2 , Linos Vandekerckhove 1 , Sarah Gerlo 1 , Marie-Angélique De Scheerder 2 1 HIV Cure Research Center, Ghent University, Ghent, Belgium, 2 Ghent University Hospital, Ghent, Belgium Background: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. The Rumba study is the first randomized clinical trial evaluating the impact on the viral reservoir, inflammation and metabolic parameters of switch from a 2nd generation integrase inhibitor (INSTI)-based triple ART regimen towards DTG/3TC vs. B/F/TAF. Results at 48 weeks confirm the effectiveness and safety of switch to DTG/3TC. Here, we quantified the mean change in inflammatory markers and immune cell counts between baseline and week 144 as an exploratory objective. Methods: In this phase 4, prospective controlled switch trial, participants with HIV-1 RNA<50 copies/ml plasma at least 3 months on any stable 2nd generation INSTI-based triple ART were randomized 2:1 to switch to DTG/3TC (N=89) or to switch or stay on B/F/TAF (N=45). Plasma viraemia was quantified via the Cobas AmpliPrep-Cobas TaqMan HIV-1 test, D-dimers via immunoturbidimetry, cytokines via Meso Scale Discovery and immune cells via Sysmex/flow cytometry. Statistical analysis was performed with linear regression on log transformed data, adjusted for baseline responses, CD4/CD8 ratio, smoking status and age. Results: Baseline characteristics were well balanced between the treatment groups, except for peak viral load (Table 1). Data were available for 103 participants at W144 (73 DTG/3TC; 30 B/F/TAF), no discontinuation was reported due to virological failure. Virological success was high, with all participants having a viral load <50 copies/ml at W144. The relative changes from baseline of inflammatory markers sCD14, sCD163, TNF-α, IL-8, IL-10, IL-21, CXCL-1, IP-10, VCAM-1, CRP and D-dimer did not differ between the treatment groups, both in the complete case and multiple imputation analyses. sCD14 decreased by 17% [CI 9-17%] in DTG/3TC and 10% [3-17%] in B/F/TAF. Furthermore, we observed no significant differences between the groups for CD4, CD8 and monocyte counts/µl whole blood. Conclusions: The Rumba W144 data confirms that switch to DTG/3TC does not appear to have a negative impact with regard to viral suppression, inflammatory markers and immune cell counts. We did not observe significant differences in these exploratory outcomes between B/F/TAF and DTG/3TC. The figure, table, or graphic for this abstract has been removed.

and TDF at baseline (8.2%, 95%CI 0.1 to 16.2). There were significant lower proportions of PWH with >5% weight gain with DTG/3TC vs BIC/F/TAF in the following subgroups ( Figure ): females (-22.5%, 95%CI -37.9 to -7.1), age 35-50 years (-15.5%, 95%CI -29.0 to -2.1), Latin-American ethnicity (-16.9%, 95%CI -33.3 to -0.4), no prior AIDS (-9.5%, 95%CI -17.9 to -1.1), and pre-switch CD4 cells ≥500/mm3 (-10.4%, 95%CI -18.9 to -1.8), TDF- (-21.1%, 95%CI-34.2 to -8.0), FTC- (-13.0%, 95%CI-22.0 to -3.9), and NNRTI-containing regimens (-16.9%, 95%CI-27.8 to -6.0). Conclusions: Although these results should be interpreted with caution as analyses were unadjusted, non-inferiority of DTG/3TC vs BIC/FTC/TAF and the difference in favor of less weight gain with DTG/3TC were generally consistent across all subgroups analyzed.

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Poster Abstracts

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Inflammatory Signatures Among People With HIV Initiating DTG/3TC vs BIC/F/TAF in the CoRIS Cohort Claudio Díaz-García 1 , Sergio Serrano-Villar 1 , Laura Luna 1 , Adriana Pinto Martínez 2 , Cristina Diez 3 , Luz Martín-Carbonero 4 , Miguel Angel Goenaga 5 , Manuel Sánchez Robledo 6 , Sergio Reus 7 , Santiago Moreno 1 , Elena Moreno del Olmo 8 , Javier Martínez-Sanz 8 , for the Cohorte de la Red de Investigación en Sida (CoRIS) 1 Hospital Universitario Ramon y Cajal, Madrid, Spain, 2 Fundación para la Investigación Biomédica Hospital 12 de Octubre, Madrid, Spain, 3 Hospital General Universitario Gregorio Marañón, Madrid, Spain, 4 Hospital Universitario La Paz, Madrid, Spain, 5 Hospital Donostia, San Sebastián, Spain, 6 Centro Sanitario Sandoval, Madrid, Spain, 7 Hospital General Universitario de Alicante, Alicante, Spain, 8 Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain Background: Persistent immune activation underlies the increased risk of comorbidities during HIV treatment. Limited evidence exists on whether initiating treatment with two drugs differs from three-drug regimens in this regard. Here, we investigated the effects of DTG/3TC vs. BIC/F/TAF on inflammatory signatures in a large prospective cohort of ART-naive people living with HIV (PWH). Methods: We included PWH who initiated DTG/3TC or BIC/F/TAF within the Spanish CoRIS cohort and had available plasma samples at month 0 (before ART initiation) and month 24 (±6). We matched participants starting each regimen 1:1 by propensity score (PS). The covariates included age, sex, and baseline CD4/CD8 ratio and HIV-1 RNA. Proteomic profiling was performed by Proximity Extension Assay using an inflammation-specific panel (Olink Target 96 Inflammation). Differences between treatment groups and timepoints were analyzed by Welch two sample t-test and paired t-test, respectively. Gene Set Enrichment Analysis (GSEA) was performed to investigate differential pathways between groups. P-values were adjusted by false discovery rate (Benjamini & Hochberg). Results: We analyzed 148 PS-matched participants and 78 proteins. The median age was 37 years, 92% male, 74% MSM, with a median baseline CD4 of 380 cells/μL and CD4/CD8 of 0.5. Differential expression analysis showed overexpression of 11 proteins in the BIC/F/TAF group at baseline. Notably, after two years of ART, these signals were no longer detectable. When compared separately, the expression of different sets of inflammatory proteins strongly decreased in both groups. Proteins such as CXCL9, CXCL11, and CD6 —associated with pathogen response— were underexpressed in both groups after two years of ART. Functional evaluation of differentially expressed proteins supported the relevance of biological processes such as cell adhesion, activation of T cells, and general activation of immune response.

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Impact of ART Simplification With Dolutegravir and Lamivudine on the HIV Reservoir Céline Fombellida-Lopez 1 , Ellen Östling 2 , Diego Aguilar Ortmans 1 , Patricia Dellot 3 , Nicole Maréchal 3 , Céline Vanwinge 1 , Aurélie Ladang 3 , Etienne Cavalier 3 , Fabrice Susin 3 , Dolores Vaira 3 , Marie-Pierre Hayette 3 , Catherine Reenaers 3 , Michel Moutschen 3 , Alexander Pasternak 2 , Gilles Darcis 3 1 University of Liège, Liege, Belgium, 2 University of Amsterdam, Amsterdam, Netherlands, 3 Liege University Hospital, Liege, Belgium Background: Antiretroviral therapy (ART) suppresses HIV replication and prevents the development of AIDS. However, ART is not curative. Persistence

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