CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Both women and men experienced a statistically significant weight loss; women (70% Black) lost weight at a rate of -1.67 kg/year (95% CI: -3.32, -0.02), and men at a rate of -0.60 kg/year (95% CI: -1.12, -0.08). Among those who had the same INSTI-TAF combination throughout, there was a statistically non-significant trend toward weight loss. When EFV and TDF were absent both before and after DOR start, DOR was statistically significantly associated with weight loss. Conclusion: In one of the first real-world analyses of weight changes among virologically suppressed individuals who started a DOR-based regimen in the US, DOR was associated with a modest but statistically significant weight loss overall. Weight loss in women is of particular significance given that weight gain has often been associated with female sex. These findings are clinically meaningful given that most individuals included were overweight or obese at DOR start. The figure, table, or graphic for this abstract has been removed. Predictors of Weight Gain in the ADVANCE, NAMSAL, and WRHI trials: EFV, TDF, and Baseline CD4 Count Andrew Hill 1 , Bryony Simmons 2 , Francois Venter 3 , Alexandra Calmy 4 , Eric Delaporte 5 , Tamara Tovar-Sanchez 6 , Charles Kouanfack 7 , Mireille Mpoudi Etame 7 , Godspower Akpomiemie 3 , Bronwyn Bosch 3 , Simiso Sokhela 3 1 University of Liverpool, Liverpool, United Kingdom, 2 Health Economics and Epidemiology Research Office, Johannesburg, South Africa, 3 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 4 University Hospitals of Geneva, Geneva, Switzerland, 5 University Hospital Montpellier, Montpellier, France, 6 Centre Hospitalier Universitaire de Montpellier, Montpellier, France, 7 Central Hospital of Yaoundé, Yaoundé, Cameroon Background: Weight gain is common during first-line ARV treatment, especially among women and those of black race. Use of TDF or EFV can suppress weight gain. People with lower baseline CD4 count show greater weight gains, but this might be from regaining weight lost during advanced disease. Methods: Data were pooled from three clinical trials: ADVANCE (n=1053), NAMSAL (n=624), and WHRI001 (n=536). These randomised trials evaluated first-line ARV regimens (TAF/XTC/DTG, TDF/XTC/DTG, and TDF/XTC/EFV) in Cameroon and South Africa. BMI over 96 weeks was analysed, stratified by baseline CD4 count as a marker for disease stage (<100, 100-200, 200-350, ≥350 cells/uL). Multivariate models at week 96 assessed factors associated with BMI and clinical obesity (BMI ≥30), adjusting for baseline CD4 category, age, sex, TDF, EFV, and clinical trial. Results: At baseline, mean age was 34.5 (SD 8.9), 60% were female, 14% had CD4 <100 cells/uL, and 31% had CD4 ≥350. Lower baseline BMI was strongly correlated with lower baseline CD4 count (p<0.001). At week 96, mean unadjusted BMI change was highest in the <100 CD4 group (+3.2 kg/m 2 ; SD 3.1) and lowest in the CD4≥350 group (+1.1; SD 2.4). Individuals with advanced disease on TAF-based regimens experienced greater BMI increases compared to those on TDF-based regimens (Figure 1). For participants on TAF-based treatment (ADVANCE only), increases in BMI to Week 96 were significantly higher in people with CD4<100 (+5.0; SD 3.1) compared to the ≥350 group (1.6; SD 2.2). In the adjusted model, for people taking TAF/FTC/DTG, BMI at Week 96 was significantly higher for people with baseline CD4<100 (28.4 [95%CI 26.7-30.1]) compared to CD4≥350 (25.3 [95%CI 24.4-26.3]; p=0.001). However, on TDF or EFV-based regimens, there was no difference in BMI across the CD4 categories. Analyses using clinical obesity (BMI >30 kg/m 2 ) showed consistent results: people taking TAF/FTC/DTG with CD4<100 were significantly more likely to become obese after 96 weeks of first-line treatment. Conclusion: For people taking TAF/FTC/DTG, baseline CD4<100 cells/uL at treatment initiation was associated with significantly higher BMI and clinical obesity at Week 96. Weight continued to rise over time for people with low CD4 counts taking TAF/FTC/DTG, above the levels seen with higher baseline CD4 counts. Use of TDF and EFV were associated with smaller rises in weight. Effective weight management is required with current regimens to avoid complications associated with significant weight increases.

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The Relationship Between Plasma Oxylipins and InSTI-Associated Weight Gain in Women Living With HIV Chin-An Yang , Cyra C. Mehta, Qian Yang, Tsungirirai Maramba, Igho Ofotokun, Kehmia Titanji, Anandi N. Sheth, Kristal M. Maner-Smith, Thomas R. Ziegler, Cecile D. Lahiri, Jessica A. Alvarez Emory University, Atlanta, GA, USA Background: Initiating or switching to integrase strand-transfer inhibitors (INSTIs) for HIV is associated with body weight gain, particularly in women. However, the specific mechanisms driving this effect remain unclear. Previous findings have implicated omega-6-derived poly-unsaturated fatty acids (PUFAs) as potential mediators of increased adiposity in people without HIV. This study investigated the relationship between INSTI-associated weight gain and plasma oxylipins, downstream PUFA metabolites, in women living with HIV (WLH) by utilizing a targeted lipidomics approach in a longitudinal design. Methods: Virologically suppressed (<200 c/mL) WLH from the Atlanta Women's Interagency HIV Study (WIHS) on antiretroviral therapy were grouped based on INSTI usage and weight change during the follow-up period (weight gain defined as ≥5% change, or weight maintenance as <5% change from baseline). We leveraged stored blood samples collected at three time points: 6-12 months before switching to or adding INSTI (baseline), 1-6 months post switch/add, and 1-2 years post switch/add, with comparable time points in the non-INSTI group. Targeted lipidomics assessed 40 oxylipins via liquid chromatography-mass spectrometry, and differences between groups assessed using linear mixed models. Results: Sixty women, aged 28-62 years, were included (n=33 INSTI, n=27 non-INSTI) with n=15 weight gainers in the INSTI group and n=9 weight gainers in the non-INSTI group. Fifty-six women identified as Black, 3 as White, and 1 as Hispanic. Within the INSTI group, nine oxylipins differed between weight gainers and maintainers over time (p-value < 0.05, Figure). Three oxylipins, linoleoyl ethanolamide (LEA), arachidonoyl ethanolamide (AEA), and 9-HpODE also differed between weight gainers and maintainers among women in the non-INSTI group. Six oxylipins were unique to those who switched to INSTI, including α-linolenoyl ethanolamide (ALEA), palmitoyl ethanolamide (PEA), oleoyl ethanolamide (OEA), 9-HODE, 9-HOTrE, and prostaglandin E2 glycerol ester (PGE2-G). Conclusion: Employing a targeted lipidomics approach, six oxylipins were linked to INSTI-associated weight gain in WLH. Among these oxylipins, ALEA and OEA have been previously implicated in weight gain processes in healthy adults, while 9-HODE and 9-HOTrE have been linked to weight gain in mouse models. Further research is needed to identify oxylipin profiles unique to INSTI usage and to determine potential underlying biological mechanisms for INSTI associated weight gain.

Poster Abstracts

CROI 2024 245