CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

795

Factors Linked to Reduced Myocardial Flow Reserve in HIV Using 82Rb Positron Emission Tomography Samantha Sithole , Serena Spudich, Mehran Sadeghi, Edward J. Miller, Attila Feher, Phillip Chan Yale University, New Haven, CT, USA Background: Despite stable HIV suppression and substantial immune reconstitution through antiretroviral therapy, people with HIV (PWH) demonstrate an elevated risk of coronary artery disease (CAD) and elevated levels of endothelial injury markers. Myocardial flow reserve (MFR) is an indicator of coronary microvascular dysfunction and overall vascular health. This retrospective study sought to evaluate the association between HIV-related parameters and MFR, determined by the stress over rest myocardial blood flow (MBF) using 82Rubidium positron emission tomography (82Rb PET) in PWH. Methods: Seventy-two PWH underwent dynamic rest/stress 82Rb PET using a hybrid PET 64-slice CT scanner (Discovery 690, GE Healthcare) at Yale New Haven Hospital for clinical indications between Nov 2016 and Apr 2022. Their global MFR was stratified into three categories: low (≤1.5), borderline (1.5-2.0), or normal (>2.0). Plasma HIV-1 RNA levels, nadir CD4+ T-cell and proximal CD4+ and CD8+ T-cell counts were collected from electronic records; 69/72 (95%) had proximal blood tests taken within 6 months before and 3 months after the scan date. The correlation between clinical and HIV-related factors and MFR was evaluated using Mann-Whiteny U test and Spearman correlation as appropriate. Results: Participants included 45 (61%) males, with a median age of 59 [IQR 53,64]; 67 (91%) were virally suppressed (<50 cps/ml). Their CD4+ and CD8+ T-cell counts were 572 [IQR 371,820] and 713 [IQR 438,981] cells/mm 3 , with a CD4/CD8 ratio of 0.91 [IQR 0.67,1.21]. Their nadir CD4+ T-cell count was 282 [IQR 133,361] cells/mm 3 . The resting and stress MBF were 0.94 [IQR 0.71,1.16] and 2.11 [IQR 1.65,2.42] ml/min/g, respectively, while the MFR was 2.21 [IQR 1.84,2.63]. Forty-five (61%) had a normal global MFR, while 9 (12%) had a low MFR. In the entire group, a lower MFR was associated with chronic kidney disease (CKD, p=0.024) and CAD (p=0.025), but not with age, sex, body mass index, HIV suppression, hypertension, diabetes mellitus, hyperlipidemia, congestive heart disease, stroke or peripheral vascular disease. PWH with low MFR had lower CD4+ T-cell (median 364 [IQR 333,634] vs. 621 [IQR 429,866], p=0.040) and nadir CD4+ T-cell counts (median 176 [IQR 74,285] vs. 296 [IQR 192,432], p=0.017) when compared to PWH with normal MFR. Conclusion: In addition to CKD and CAD, PWH who have lower nadir and current CD4+ T-cell counts, indicating a more compromised immune function, may be at a higher risk of coronary microvascular dysfunction.

to sacrifice, animals were intravenously injected with the fluorescent dye BSA-FITC and hearts were excised and evaluated for microvascular leakage/ density of perfused microvessels, and fibrosis. Western blot assays and immunofluorescence and biochemical assays were also conducted. Results: At the end of the protocol, echocardiography revealed E:A, E:e', left atria volume, global longitudinal and right ventricular diameter-systole increased by 32.1±5.1%, 28.2±5.6 %, 26.6±4.2, 32.5±4.3% and 19.6±1.3%, respectively in Hu-mice treated DTG/TDF/FTC compared to uninfected controls. Photoacoustic imaging also showed a 30.4±6.8% reduction in saturated oxygenated hemoglobin in the anterior wall of the heart. Ex vivo analyses of hearts from DTG/TDF/FTC-treated HIV mice revealed a 37.3±8.2% reduction in intact microvessels, a 30.6±6.2% reduction in the density of perfused microvessels with regions of micro-ischemia There were also 20.2±1.2 and 20.6± .3 % increases in interstitial and perivascular fibrosis, respectively. Expression of hypoxia-induced transcription factor HIF-1α was increased 2.6±0.5-fold, the cytotoxic glycolysis metabolite, methylglyoxal (MG) was increased 3.2±0.3-fold and the inflammation-induced protein, vascular adhesion protein-1 was increased 123.5±10% in hearts of HIV-infected female Hu-mice compared to uninfected controls Conclusion: These new data show that HIV-infected Hu-mice treated with DTG/ TDF/FTC can recapitulate the diastolic dysfunction, microvascular dysfunction, and hypoxia/ischemia seen in WLHV. It also provides a model to study diastolic dysfunction in HIV infection. R01HL164306 The figure, table, or graphic for this abstract has been removed. Impact of Semaglutide on Weight Change Among People With HIV: A Stratified Analysis by Baseline BMI Lara Haidar 1 , Heidi M Crane 2 , Robin M. Nance 2 , Allison R. Webel 2 , Geetanjali Chander 2 , Bridget Whitney 2 , Amanda Willig 3 , Lyndsey S. Mixson 2 , Alekhya Lavu 1 , Laila Aboulatta 1 , Mindy Dai 2 , Andrew Hahn 2 , Edward Cachay 4 , Lydia N. Drumright 2 , Sherif Eltonsy 1 1 University of Manitoba, Winnipeg, Canada, 2 University of Washington, Seattle, WA, USA, 3 University of Alabama at Birmingham, Birmingham, AL, USA, 4 University of California San Diego, San Diego, CA, USA Background: Limited real-world evidence on effectiveness of semaglutide for weight loss among people with HIV (PWH) exists. We aimed to investigate weight change in a cohort of PWH initiating semaglutide use. Methods: Adult PWH who initiated semaglutide between 2018 and 2022 and had ≥2 weight measurements from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort were assessed for within-person (1) bodyweight change in kg at 1 year and (2) percent bodyweight change using linear mixed model adjusted for age, sex, race/ethnicity, CNICS site, diabetes status, CD4 cell count, HIV viral load (VL), and time. We also investigated whether the effect of semaglutide on weight change varied by baseline BMI category, diabetes status, and semaglutide dose. Results: During the study period 222 PWH initiated semaglutide. Mean follow up was 1.1 years. Approximately 75% were male. At baseline mean age was 53 years (standard deviation [SD]: 10), average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (VL< 50 copies/mL). The majority, 87 (69.6%) received low doses of subcutaneously injected semaglutide (0.25, 0.5, and 1 mg), while 24 (19.2%) received high doses of subcutaneously injected semaglutide (1.7, 2, and 2.4 mg). In linear mixed models, treatment with semaglutide was associated with an average weight loss of 6.5 kg at 1 year (95% CI -7.7, -5.2) and with a percent bodyweight reduction of 5.7% (-6.9 to -4.6) at 1 year. Reductions in weight among PWH were -4.1 (-7.9, -0.2) kg (p =0.04) with normal BMI, −4.6 (−6.9, −2.3) kg (p< 0.001) in overweight, −5.4 (−7.3, −3.4) kg (p< 0.001) in obesity class 1, −7.6 (−9.5, −5.7) kg (p< 0.001) in obesity class 2, and −8.8 (−10.9, −6.7) kg (p< 0.001) in obesity class 3. There was a significant difference in weight loss between PWH with obesity class 3 (reference) and PWH with normal BMI, overweight, and obesity class 1 (p for interaction <0.05). No significant differences in weight loss by diabetes status or semaglutide dose were observed. Conclusion: Among PWH, semaglutide was associated with significant weight loss, with more substantial weight loss observed in individuals with higher BMI. These findings are highly relevant given high proportions of diabetes, overweight, and obesity among PWH.

797

Poster Abstracts

796

Diastolic Dysfunction With Preserved Ejection Fraction in Humanized HIV-Female Mice on cART Keshore R Bidasee , Prasanta Dash, Fadhel A. Alomar, Zachary L. Venn, Chen Zhang, Rongyue Tu, Lili Guo, Bryan T. Hackfort, Santhi Gorantla University of Nebraska Medical Center, Omaha, NE, USA Background: Early-onset diastolic dysfunction has emerged as a major threat to healthy aging in people with HIV-1 infection. Women living with HIV-1 infection (WLWH) are especially vulnerable and develop a unique pattern vascular and myocardial ischemia compared to men. Animal models that recapitulate this pathophysiology remain unreported, and this has left a void in our understanding of the molecular causes of the disease and treatment strategies to alleviate it. Methods: Female NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice) were infected with HIV-1ADA and treated for fourteen weeks with dolutegravir (DTG)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) starting two weeks of infection. In vivo echocardiography was used to assess cardiac function and dimensions. Photoacoustic imaging was used to assess saturated oxygenated hemoglobin in the anterior wall of the heart, Prior

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