CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: Viral suppression was associated with significantly reduced inflammation in treatment-naïve PWH, with no significant differences in selected inflammatory biomarkers among the three ART regimens during the 144-week randomized period and each was sustained after the open label switch to B/F/TAF. Viral blips were associated with increases in some of the markers. The small number of available samples limited this study, thus the findings warrant additional investigation.

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Impact of Raltegravir Intensification on the Gut Microbiota of People With Chronic HIV-1 Infection Maria Casadellà , Aleix Elizalde-Torrent, Francesc Català-Moll, Alessandra Borgognone, Mariona Parera, Marc Noguera-Julian, Roger Paredes IrsiCaixa Institute for AIDS Research, Badalona, Spain Background: Chronic human immunodeficiency virus 1 (HIV-1) infection is associated with gut microbiota alterations, including low gene richness and shifts in certain bacterial species, which have been linked to immune dysfunction. Residual HIV-1 replication might contribute to perpetuating such gut dysbiosis. We sought to explore if antiretroviral treatment (ART) intensification with raltegravir (RAL) had the ability to modify the gut microbiome composition and related immune parameters. Methods: This was a prospective, double-blind, placebo-controlled, 2-arm randomized trial, where aviremic subjects with HIV-1 under stable NNRTI- or PIr-based ART were randomized 2:1 to add RAL (1200 mg QD) or placebo to their ongoing ART, stratified by NNRTI vs PIr ART at study entry. We evaluated the longitudinal effect of RAL intensification on the gut microbiome by shotgun metagenomics as well as on soluble markers of immune activation and gut integrity (sCD14, DDimer, IFABP, IP10, and LBP) and cellular markers of immune activation and maturation (HLA-DR, CD38), exhaustion (PD-1) and senescence (CD57) at weeks 0, 12, 24 and 48. Non-parametric paired and unpaired tests and Linear Mixed Models (LMM) were used to analyse the data as needed. Results: Fifty-seven subjects were included, 38 received RAL and 19 placebo. Microbial gene richness did not change in subjects receiving RAL but increased in those receiving Placebo (LMM p=0.009). There were no differences in beta-diversity between groups. In subjects receiving RAL, 3 Roseburia species (R. hominis, intestinalis and unilivorans) decreased over time, whereas Bifidobacterium longum and Paraprevotella xylaniphila increased. Treatment intensification was associated with lower Streptococcus termophilus abundance than placebo from week 12 onwards. All subjects remained aviremic throughout the study. RAL intensification was not associated with changes in CD4+, CD8+, sCD14, DDimer, IFABP, IP10, or LBP. In the placebo arm, we observed longitudinal increases in HLADR+ effector memory and TEMRA CD8+ T-cells, as well as in CD38+ Naïve CD4+ and CD57+ TEMRA CD4+ T-cells. Additionally, we noted decreases in CD57+ TEMRA CD8+ T-cells. No changes in cellular markers occurred in the RAL arm. Conclusion: RAL intensification of PI/r or NNRTI-based regimens is associated with reduced immune activation and senescence in CD8+ T-cells, coupled with minor changes in the gut microbiome composition. Blood Telomere Length in ART-Naive PLWH Starting DTG+3TC vs Triple Regimen With 2 Nucleosides Francesca Lombardi 1 , Alessia Sanfilippo 2 , Massimiliano Fabbiani 3 , Alberto Borghetti 1 , Arturo Ciccullo 4 , Valentina Iannone 2 , Damiano Farinacci 1 , Pierluigi Francesco Salvo 2 , Enrica Tamburrini 2 , Simona Di Giambenedetto 2 1 IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy, 2 Catholic University of the Sacred Heart, Rome, Italy, 3 Azienda Ospedaliera-Universitaria Senese, Siena, Italy, 4 Ospedale San Salvatore - L'Aquila, L'Aquila, Italy Background: People living with HIV (PLWH) show a marked shortening of blood telomere length (BTL) early after seroconversion. This is caused by uncontrolled viral replication with sustained immune activation, immunosenescence and inhibition of telomerase by HIV proteins. Antiretroviral

Poster Abstracts

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Inflammatory Profile of B/F/TAF, DTG/ABC/3TC, and DTG+F/TAF Over 5 Years and Effects of Viral Blips Nicholas Funderburg 1 , Susie S. Huang 2 , Calvin Cohen 2 , Kate Ailstock 1 , Jean Lee 2 , Brenda Ng 2 , Kirsten White 2 , Jeff J. Wallin 2 , Bryan Downie 2 , Grace A. McComsey 3 1 The Ohio State University, Columbus, OH, USA, 2 Gilead Sciences, Inc, Foster City, CA, USA, 3 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: Elevated levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after suppression of HIV-1 replication below the limit of detection by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on biomarkers of inflammation are needed. Additionally, it remains unknown whether transient elevations of viral load ("blips") during ART are associated with increases in inflammatory biomarkers. This study analyzed the effect of ART on selected biomarkers of inflammation and immune activation. Methods: We utilized cryopreserved samples from treatment-naïve PWH enrolled in two Phase 3 clinical studies investigating the efficacy and safety of B/F/TAF, DTG/ABC/3TC and DTG+F/TAF over a 5-year window (GS-US-380 1489/1490). At wk144, participants were switched to open label B/F/TAF. We measured levels of interleukin-6 (IL-6), C-reactive protein (hsCRP), D-dimer, soluble CD14 (sCD14), and tumor necrosis factor-α receptor 1 (TNFR1) by ELISA from select baseline, wk 24, 48, 144, and 240 samples (B/F/TAF, N=123; DTG/ ABC/3TC, N=62; DTG+F/TAF, N=58). Samples from PWH who experienced a viral blip (n=44, defined as single VL>50c/mL) were also analyzed and paired with the most recent suppressed sample. Longitudinal biomarker changes were assessed using a constrained mixed effects linear regression model adjusting for covariates. Results: Baseline demographics and selected laboratory characteristics were similar across studies. Significant decreases in D-dimer, sCD14, and TNFR1 were observed in all treatment arms, with no significant differences between arms at any timepoint. Similarly, biomarker levels also remained stable following ART switch at week 144. No significant changes in hsCRP or IL-6 were observed in any arm at any timepoint. In the analysis of viral blips, a significant association was observed between sCD14 and increasing viral load (p=0.022); a similar trend was seen with D-dimer

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