CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

antiretrovirals (ARV), dummy variables were created, with no ARV taken at BL and 5-year follow-up (5YFU) as reference. Results: 1186 participants (mean age 49.4±11.3 years, 87% Caucasian, 16.9% females, 2% ART naïve) were included in the analysis. Mean weight increased from 77.2±14.8 to 89.8±17.2kg and from 79.2±15.7 to 79.5±15.8kg within 5 years in groups A and B, respectively. Regression models are shown in Figure 1. Increasing age showed associations with a decreased risk for weight gain (OR 0.970 [95%Cl 0.954-0.985] per SD). Prevalent lipoatrophy was associated with a lower risk of weight gain (OR 0.547 [95%Cl 0.286-0.980]). An increase in CD4/ CD8 ratio was associated with increased risk of weight gain (OR 1.281 [95%Cl 1.101-1.489]). PIs taken at BL and 5YFU compared to no PIs taken at BL and 5YFU were associated with less weight gain (OR 0.479 [95%Cl 0.293-0.756]). Overall, NNRTI, NRTI, and INSTI were not associated with increased or decreased risk. Among specific ARVs analysed ), switch to TAF after BL was associated with an increased risk for ≥10% weight gain (OR 1.550 [95%Cl 1.088-2.204]), while TDF taken at BL and 5YFU shows a decreased risk (OR 0.673 [95%Cl 0.413-1.068]). Conclusions: Younger age and increasing CD4/CD8 ratio were associated with ≥10% weight gain over 5 years. Continuous use of PIs was associated with a lower risk of weight gain, while no significant association of NNRTI or INSTI intake with ≥10% weight gain was observed over 5 years. Switching off TDF showed a trend towards increased weight gain. Switching to TAF after BL was associated with an increased risk for ≥10% weight gain. The figure, table, or graphic for this abstract has been removed. Serum Metabolomic Signatures Associated With InSTI-Related Weight Gain in Women With HIV Chin-An Yang 1 , Young-Mi Go 1 , Brahmchetna Bedi 1 , Cyra C. Mehta 1 , Ighovwerha Ofotokun 1 , Anandi N. Sheth 1 , Mohammed K. Ali 1 , Maria L. Alcaide 2 , Frank Palella 3 , Jordan E. Lake 4 , Leah H. Rubin 5 , Deborah Konkle-Parker 6 , Anjali Sharma 7 , Cecile D. Lahiri 1 , Jessica A. Alvarez 1 1 Emory University, Atlanta, GA, USA, 2 University of Miami Miller, Miami, FL, USA, 3 Northwestern University, Chicago, IL, USA, 4 University of Texas Health Science Center at Houston, Houston, TX, USA, 5 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 6 University of Mississippi Medical Center, Jackson, MS, USA, 7 Albert Einstein College of Medicine, Bronx, NY, USA Background: Initiation of integrase strand-transfer inhibitors (INSTIs) is associated with body weight gain in women with HIV (WWH); however underlying mechanisms are unclear. Leveraging samples from the Women’s Interagency HIV Study (WIHS) cohort, we performed serial high-throughput untargeted metabolomics to determine metabolic signatures associated with INSTI-related weight gain. Methods: This study included virologically suppressed (<200 c/mL) WWH on antiretroviral therapy (ART) and women without HIV (WWoH) enrolled in WIHS. We compared weight change among WWH who switched/added an INSTI with those who remained on non-INSTI ART and with WWoH (weight gain, defined as ≥5% change from baseline, versus weight maintenance, defined as <5% change). Serum samples were collected from three time points: 6-12 months prior to switching to or adding an INSTI (baseline), 1-6 months post-switch/ addition, and 1-2 years post-switch/addition, with equivalent time points for the non-INSTI and WWoH. Samples were analyzed with liquid chromatography mass spectrometry-based high-resolution metabolomics (HRM). Differences between weight change groups were assessed using linear mixed-effect models, adjusted for baseline age and body mass index (BMI) and stratified by ART exposure. Metabolic pathway enrichment analysis was performed on significant metabolites using the mummichog algorithm. Results: N =191 women, aged 25-70 years, were included (n=37 INSTI, n=88 non-INSTI, n=66 WWOH; 70% Black; 30% White or other ethnicities). In the INSTI group, 830 metabolites enriched within 12 metabolic pathways differed between weight gainers and maintainers ( p <0.05). INSTI-specific pathways included n-3 polyunsaturated fatty acid (PUFA), linoleic acid (LA) oxylipin, and leukotriene metabolism ( p <0.05, Table), wherein most of metabolites were higher at baseline in weight maintainers and remained elevated. Eicosapentaenoic acid metabolism differed by weight gain in the non-INSTI group. In WWOH, no PUFA or oxylipin-related metabolism was found, except for LA, which was enriched in de novo fatty acid biosynthesis. Conclusions: Untargeted HRM identified pathways related to anti- and pro-inflammatory lipid metabolism that were specific to INSTI-related weight gain, indicating a metabolic profile that may be vulnerable to weight gain after

INSTI switch/addition for WWH. Further research is needed to reveal underlying biological mechanisms of INSTI-related weight gain.

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Weight Change in Trial of Switching From Second-Line bPI to B/F/TAF in a Context of Food Insecurity Fabienne Homeus 1 , Samuel Pierre 1 , Jean Bernard Marc 1 , Jodany Bernadin 1 , Vanessa Rivera 1 , Sean E. Collins 2 , Letizia Trevisi 3 , Abigail Zion 4 , Adina Zhang 4 , Elizabeth Fox 5 , Jean W. Pape 1 , Serena Koenig 3 , Vanessa Rouzier 1 1 GHESKIO Center, Port-au-Prince, Haiti, 2 Gilead Sciences, Inc, Foster City, CA, USA, 3 Brigham and Women's Hospital, Boston, MA, USA, 4 Analysis Group, Inc, Boston, MA, USA, 5 Cornell University, Ithaca, NY, USA Background: Data are limited on weight gain after switching from second-line boosted PI-based regimens to B/F/TAF in low and middle-income countries (LMICs). We assessed weight in a clinical trial that compared continuing boosted PI + NRTIs vs. B/F/TAF during a period of severe civil unrest in Haiti. Methods: The parent study was a prospective, open-label trial conducted at GHESKIO in Port-au-Prince, Haiti. Adults (³18 years) with viral suppression on second-line PI/r-based ART were randomized to continue their current regimen vs. switch to B/F/TAF. In this secondary analysis, we assessed weight gain and food insecurity. Results: Between October 2020 and April 2023, 301 participants were enrolled and randomized (B/F/TAF: 153; bPI: 148). Median age was 49 years (IQR 42, 56), 173 (57%) were women, the median BMI was 23.3 kg/m 2 (IQR 20.8-27.1) and 28 (9%) had BMI <18.5. At enrollment, 175 (60%) were taking lopinavir/r and 115 (40%) atazanavir/r; 226 (78%) were taking tenofovir disoproxil fumarate, 51 (18%) zidovudine, and 13 (4%) abacavir; all were taking lamivudine or emtricitabine. At Week 48, the median change in weight was +1.7kg (IQR: -0.6, +5.1) in the B/F/TAF and -1.1kg (IQR: -2.9, +1.1) in the bPI group (p<0.001). In the B/F/TAF group, median weight gain was higher in females than males (+2.9 kg vs. +0.6 kg; p<0.001), and 21.7% of females vs. 8.2% of males (p<0.001) gained ³10% body weight (Table 1). In contrast, the bPI group had median weight loss of -0.8kg in females and -1.7 kg in males. In the total cohort, the proportion of participants with severe food insecurity increased from 40.1% at enrollment to 49.2% at 48 weeks (p<0.001). There was no difference in the proportion with severe food insecurity at enrollment or 48 weeks by group. Conclusions: Weight gain was common among females who switched from PI/r-based regimens (78% included TDF) to B/F/TAF, in the context of high rates of food insecurity. This is consistent with findings of similar drug switches in other settings. In contrast, we observed weight loss in the standard of care group, which may have different clinical implications in settings with high rates of food insecurity. Understanding the implications of weight gain after stopping TDF is essential to guide global policies on TDF-sparing regimens.

Poster Abstracts

CROI 2025 278