CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

or (3) a self-reported use of anti-diabetes medications. Associations between HIV status, sleep apnea severity, and prevalent diabetes were assessed using multivariable logistic regression models adjusted for age, race, BMI, and family history of diabetes. Results: MWH were younger (median age: 56 years vs. 62 years; p < 0.001) and more likely to be non-white (43.9% vs. 23.1%; p < 0.001); BMI was similar by HIV status (median: 27 kg/m 2 ). MWH and MWOH had similar crude prevalences of sleep apnea (52.7% vs. 54.0%, respectively; p = 0.74) and diabetes (21.5% vs. 19.4%, respectively; p = 0.47). The adjusted prevalence of diabetes was significantly greater among men with severe sleep apnea and HIV than among men with severe sleep apnea and no HIV (41.2% vs. 23.7%, respectively; p = 0.046). No significant interaction between HIV status and sleep apnea severity on prevalent diabetes was observed. In models restricted to MWH, duration (years) of protease inhibitor use was independently associated with prevalent diabetes (aOR: 1.05; 95% CI: 1.01 - 1.09; p = 0.014). Conclusions: Among men with severe obstructive sleep apnea, living with HIV was associated with a higher prevalence of diabetes. These data suggest that the metabolic impact of obstructive sleep apnea is more pronounced among PWH. Impact of HIV Infection on Adipose Tissue Fibrosis and Its Association With Insulin Resistance Diana L. Alba 1 , MoonKyung Choi 1 , Alaa Abdellatif 1 , Stephen Brown Mayfield 1 , Thuy Pham 1 , David Berrios 1 , Judy Gonzalez-Vargas 1 , Antonio Rodriguez 1 , Marin Ewing 1 , Tony R. Figueroa 1 , Dawei Bu 2 , Steven G. Deeks 1 , Philipp E. Scherer 2 , Suneil K. Koliwad 1 , Peter W. Hunt 1 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Texas Southwestern Medical Center, Dallas, TX, USA Background: People with HIV (PWH) are at elevated risk for type 2 diabetes (T2D), despite viral suppression. While obesity is a well-known driver of T2D in the general population, HIV-specific factors, such as chronic inflammation and antiretroviral therapy (ART), may contribute to risk in PWH. While subcutaneous adipose tissue (SAT) fibrosis promotes insulin resistance in obesity, less is known about its role in HIV, and whether it has a distinct tissue transcriptomic profile in this setting. Methods: We studied 112 participants (43 ART-suppressed PWH and 69 without HIV) matched for BMI, age, sex, and hemoglobin A1c, from UCSF cohorts, stratified by %body fat (%BF) by DEXA (high: >35% women, >25% men). SAT fibrosis was assessed with tissue hydroxyproline (HP) levels, insulin resistance by HOMA-IR, and plasma endotrophin (a collagen VIalpha3 posttranslational cleavage product with potent pro-fibrotic activity) by ELISA. Transcriptomic analysis of SAT was performed using a Nanostring panel of 772 fibrosis-related genes. Results: PWH had more SAT fibrosis (by HP levels) than those without HIV (P<0.01), particularly among those [n=17] with normal %BF (median 68 vs 439, P=< 0.01), suggesting that the excess SAT fibrosis in PWH is not solely due to increased adiposity. In PWH, SAT fibrosis correlated more strongly with HOMA-IR in those with normal %BF (r=0.70, P<0.01) than in those with high %BF (r=0.38, p=0.07). Plasma endotrophin levels were also higher in PWH than controls (p<0.05), and positively correlated with HOMA-IR (r=0.35, p<0.01) and HP levels (r=0.34, P=0.03) in PWH. In transcriptomic analysis, PWH had a unique obesity-independent upregulation of genes such as COL14A1 , which stabilizes collagen, and CSF1R , which supports myeloid cell differentiation and whose ligand (CSF1) is associated with increased mortality in treated HIV (Figure 1). In contrast, both HIV and high %BF induced upregulation of inflammatory mediators like CCL4 and NLRP3 , highlighting some shared transcriptional pathways between obesity and HIV. Conclusions: PWH have increased SAT fibrosis, even at normal %BF, which is characterized by obesity-independent transcriptional changes. Upregulation of COL14A1 in PWH may play a pivotal role in promoting SAT fibrosis and associated metabolic dysfunction while CSF1R upregulation may suggest an important role of macrophage differentiation. Furthermore, SAT fibrosis in PWH is predictive of insulin resistance at normal %BF and can be assessed noninvasively via plasma endotrophin levels.

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Early Pregnancy Insulin Dynamics in South African Women With HIV on Dolutegravir: The ORCHID Study Julia Goedecke 1 , Georgia Roussos 2 , Kristina Utzschneider 3 , Elton Mukonda 2 , Justine Legbedze 4 , Allison Zerbe 5 , Landon Myer 2 , Elaine Abrams 6 , Hlengiwe Madlala 2 , Sandisiwe M. M. Matyesini 2 , Jody Rusch 2 , Jami Josefson 7 , Patrick Catalano 8 , Jennifer Jao 7 , for the ORCHID Study 1 South African Medical Research Council, Cape Town, South Africa, 2 University of Cape Town, Cape Town, South Africa, 3 VA Puget Sound Health Care System, Seattle, WA, USA, 4 Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA, 5 ICAP at Columbia University, New York, NY, USA, 6 Columbia University Irving Medical Center, New York, NY, USA, 7 Northwestern University, Chicago, IL, USA, 8 Massachusetts General Hospital, Boston, MA, USA Background: Little is known about glucose regulation by insulin in early pregnancy in women with HIV (WWH) receiving tenofovir/lamivudine/ dolutegravir (TLD). We assessed differences in insulin dynamics in early pregnancy in WWH receiving TLD. Methods: The ORCHID study enrolled WWH initiating/receiving TLD and HIV seronegative (HIV-) women >16 years old and <18 weeks gestational age (GA) in South Africa. Pregnant women known to have diabetes or hypertension were excluded. For this analysis we included women who enrolled at <14 weeks GA. Participants underwent a 75g oral glucose tolerance test (OGTT) to estimate insulin sensitivity (Matsuda index), 1st phase insulin response (Stumvoll equation), beta-cell function (oral disposition index, DIo), and Mari model derived measures of beta-cell function (glucose sensitivity) and postprandial insulin clearance. TLD duration was categorized as <15 (TLD <15 ) vs 15-90 (TLD 15-90 ) vs >90 (TLD >90 ) days prior to enrollment. Quantile regression was used to assess the association of 1) HIV status and 2) duration of TLD with insulin parameters, adjusting for confounders. Results: 894 women were included (357 WWH, 537 HIV-); among WWH 109 were TLD <15 , 34 TLD 15-90 , and 214 TLD >90 . WWH were older than HIV- women (median 29 vs 26 years), but their median (interquartile range) BMI [29.8 (25.0-35.0 kg/m 2 )], GA [10 (9.0-12.7 weeks)] and rates of gestational diabetes or frank diabetes at OGTT did not differ. Among WWH, 7% had CD4 <200 cells/ mm 3 and 25% HIV RNA >50 copies/mL at enrollment. After adjusting for age, BMI and socioeconomic status, WWH had higher Matsuda, Stumvoll, DIo, and Mari-derived glucose sensitivity & postprandial insulin clearance than HIV- women (all p<0.004). (Table). Compared to HIV- women, TLD <15 and TLD >90 were associated with higher Matsuda, Stumvoll, and mean postprandial insulin clearance (all p<0.05), whereas only TLD >90 was associated with higher DIo and glucose sensitivity (p<0.001 for both). Conclusions: WWH receiving TLD have higher insulin sensitivity and beta cell function than HIV-women, with higher duration on TLD having a more favorable effect on beta-cell function in early pregnancy. Our findings suggest that pregnant WWH receiving TLD may be at reduced risk for diabetes in early pregnancy compared to HIV- women. Longitudinal studies in pregnant WWH will be useful to understand whether this favorable profile persists.

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Poster Abstracts

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