CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

merit consideration when treating PLWH with additional metabolic risk factors. The figure, table, or graphic for this abstract has been removed. Phase 4 DEFINE Switch Study to Manage InSTI-related Weight Gain: Metabolics and Biomarker Analysis Johnnie Lee 1 , David Anderson 1 , Nina Ahmad 1 , Richard B. Simonson 1 , Ping Xu 2 , Briana Journée 1 , Tien-huei Hsu 1 1 Janssen Scientific Affairs, LLC, Titusville, NJ, USA, 2 Janssen Research & Development, LLC, Titusville, NJ, USA Background: Integrase strand transfer inhibitor (INSTI)–based antiretroviral therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor– or boosted protease inhibitor (PI)–based regimens, and these effects disproportionately impact Black and Hispanic individuals and women living with HIV-1. DEFINE is the first prospective, randomized trial to explore the impact of switching from an INSTI-based regimen to a PI-based regimen to mitigate or reverse INSTI-related weight gain. As previously reported, the primary Week 24 analysis found no significant difference in percent change in body weight from baseline when switching to darunavir/ cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) compared to continuing INSTI+tenofovir alafenamide (TAF)/emtricitabine (FTC). Methods: DEFINE (NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to D/C/F/TAF versus continuing INSTI+TAF/FTC in virologically suppressed adults with HIV-1 who had ≥10% weight gain while on the INSTI-based regimen. The primary objective was to assess percent change in body weight from baseline to Week 24. Metabolic and biomarker data through Week 24 are reported in this analysis. Results: Among the 103 adults who were randomized to D/C/F/TAF (n=53) or continued INSTI+TAF/FTC (n=50), 30% were female, 61% were Black/African American, and the median BMI was 32.7 kg/m 2 . Consistent with the primary endpoint, at Week 24 most participants remained classified as obese (D/C/F/ TAF, 53%; INSTI+TAF/FTC, 70%) and had experienced minimal BMI and waist circumference changes. Glucose and HbA1c values remained largely unchanged through Week 24; however, there were small decreases in insulin and HOMA-IR values in the INSTI+TAF/FTC arm (Table). No participants in either arm decreased medication dosages or entirely stopped lipid-lowering, anti-glycemic, or anti hypertensive medications through Week 24. Changes in leptin, adiponectin, and α-melanocyte stimulating hormone were minimal in both arms, as were changes in NAFLD fibrosis score. The percent of participants at high risk of NASH by HAIR score decreased in both arms. Conclusion: Consistent with the minimal body weight changes observed through Week 24, metabolic and biomarker data remained relatively stable. Metabolic parameters in this high-BMI population did not improve following antiretroviral switch, highlighting that weight gain should be a pretreatment consideration.

if used in combination with either TAF, tenofovir disoproxil fumarate (TDF), or abacavir (ABC) as backbone. We used multi-variable generalized estimating equations (GEE) to assess the association between WG and individual ARV use in the anchor and backbone category. Within each category, patients were censored if they stopped, switched, or added another ARV. We adjusted for main effects of HIV-related, demographic, substance use, and clinic utilization parameters, in addition to time, and retained only significant covariates and factors for the final model. Results: 4,194 patients contributed 6,514 patient-years and 20,528 BMI measurements. The majority were black (55%), male (77%), and non-Hispanic (72%). Median baseline BMI was 24.4, inter-quartile range (IQR) 21.6-28.2. After 3-years, median BMI was 27.1 (IQR 23.8-31.3), and median BMI gain was 1.8 (IQR 0.2-4.1). The most used ARVs were DTG (23%), EFV (22%), and DRV (14%) in the anchor, and TDF (58%), TAF (21%), and ABC (21%) in the backbone group. In the final model, within the anchor group, we found no significant WG differences in pairwise comparisons between any of the INSTIs, RIL, or protease inhibitors; the same was true for ABC and TAF in the backbone group. In contrast, both EFV and TDF were associated with significantly lower WG in all pairwise comparisons within their respective groups and were retained for the final model shown in the table. Calendar year, annual follow-up frequency, and Hispanic ethnicity did not significantly contribute to BMI change. Conclusion: Over a 15-year period, our demographically diverse patient population experienced substantial WG in the first 3 years after cART initiation. Among 11 examined ARVs, only EFV and TDF were independently associated with (decreased) WG. The figure, table, or graphic for this abstract has been removed. Lipidome Composition and Weight Changes at 48-week 3TC-DTG and FTC/TAF/BIC: Data of the ICONA Cohort Roberta Rovito 1 , Valeria Bono 1 , Camilla Tincati 1 , Matteo Augello 1 , Alessandro Tavelli 2 , Alessandra Rodanò 2 , Francesca Bai 1 , Valentina Mazzotta 3 , Andrea Antinori 3 , Eugenia Quiros-Roldan 4 , Andrea Giacomelli 5 , Giovanni Guaraldi 6 , Antonella D'Arminio Monforte 2 , Giulia Marchetti 1 , for the ICONA Foundation Study Group 1 University of Milan, Milan, Italy, 2 Icona Foundation, Milan, Italy, 3 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 4 University of Brescia, Brescia, Italy, 5 Luigi Sacco University Hospital, Milan, Italy, 6 University of Modena and Reggio Emilia, Modena, Italy Background: cART start has been associated with weight gain (WG), which entails an increased dysmetabolic risk in PLWH, the biologic correlates of which are ill defined. We assessed WG and lipidome profile in cART-naïve patients starting INSTI-based dual (DT-3TC-DTG) or triple (TT-FTC/TAF/BIC) cART. Methods: We performed untargeted lipidomic on PLWH of the ICONA cohort both prior (T0) and 48w after DT or TT cART (T1). Raw data were aligned, normalized, and ions from both modes were merged for multivariate analysis. Supervised regression modelling was performed with Orthogonal Partial Least Squares Discriminant Analysis, and significant biomarkers are selected based on variables' significance in the model (VIP>1.5), t-test (p<0.05), and fold change (FC>2), followed by pathway enrichment analysis (PEA). Results: 119 PLWH were included: 62 DT, 57 TT. At T0, DT patients were older, more frequently male, with higher CD4, lower HIV-RNA, fewer AIDS diagnoses, higher body weight and HDL, despite comparable total and LDL cholesterol, triglycerides and lipid lowering agents (Fig.1A). At T1, TT showed higher WG versus DT (5.1 ± 5.8 vs 2.2 ± 3.2Kg SD, p<0.001). Both TT and DT displayed a net separation in the OPLS-DA model between T0 and T1, witnessing substantial lipidomic changes (Fig.1B-C). In DT, 109 lipids were significantly different at T1, and 66 lipids in TT, with a higher proportion of up-regulated lipids in TT (83.3% vs 30.3%, p<0.0001) (Fig.1D-E). While both treatments resulted in glycerolipids and glycerophospholipids changes (PEA), DT mainly modified glycerolipids (diacylglycerol-DAG, monoacylglycerols-MG, monoradylglycerols-MAG), and TT glycerophospholipids (phosphatidylcholines-PC, lysophosphatidic acids-LPA). When seeking for associations between WG and lipidome, WG positively correlated with PC lipids, and negatively with DAG in TT PLWH only, with no significant correlations detected in DT. Conclusion: First-line 48-week cART substantially and differentially shapes the plasmatic lipidome composition, with 3TC/DTG mainly affecting DAG, and FTC/ TAF/BIC the PC pathways. Most interestingly, the correlation between higher WG and glycerophospholipids metabolism with potential phosphatidylcholines involvement in FTC/TAF/BIC, that is not seen in DT, suggests distinct interactions between lipidomic signature and body weight according to cART regimens, that

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Weight Gain in People With HIV (PWH) vs People Without HIV (PWoH) Over a 3-Year Period Richard A Elion 1 , Joshua Gruber 2 , Janna Radtchenko 1 , Paul E. Sax 3 , Megan Dunbar 2 , Joseph J. Eron 4 , Calvin Cohen 2 , Gregory Huhn 5 , Keri N. Althoff 6 , Grace A. McComsey 7 1 Trio Health, Inc, Louisville, CO, USA, 2 Gilead Sciences, Inc, Foster City, CA, USA, 3 Brigham and Women's Hospital, Boston, MA, USA, 4 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5 Ruth M Rothstein CORE Center, Chicago, IL, USA, 6 The Johns Hopkins University, Baltimore, MD, USA, 7 University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: The study evaluated weight (wt) change and shift in BMI class in PWH on antiretroviral therapy (ART) over 3 years (3y) vs PWoH matched on baseline (BL) characteristics.

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