CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

842

Neighborhood Vulnerability Predicts Non-Communicable Disease Risk Among People With HIV Aiwei Yan 1 , Aihua Bian 1 , Peter F. Rebeiro 1 , Megan Turner 1 , Paridhi Ranadive 1 , Chandler Shaffernocker 1 , Austin Katona 1 , Noelle Best 1 , Victor Tian 2 , Leslie J. Pierce 1 , Timothy R. Sterling 1 , Bryan E. Shepherd 1 , Jessica L. Castilho 1 , Aima Ahonkhai 3 1 Vanderbilt University Medical Center, Nashville, TN, USA, 2 Vanderbilt University, Nashville, TN, USA, 3 Massachusetts General Hospital, Boston, MA, USA Background: Social determinants of health underly persistent disparities in the rates of non-communicable diseases (NCDs) across communities but have been understudied in people with HIV (PWH). Methods: We assessed associations between the CDC's Social Vulnerability Index (SVI) and NCD burden and risk in PWH in care at the Vanderbilt HIV Clinic from Jan 2009-Dec 2019. The SVI is a census-tract-level measure of deprivation based on 16 factors, grouped into a total score and four themes (socioeconomic status, household composition/disability, minority status/language, and housing/transportation); higher SVI indicates greater neighborhood vulnerability. SVI was assigned using residence at enrollment or first visit after Jan 2009. NCDs included cardiovascular, liver, metabolic, and chronic kidney disease (stage ≥3), as well as non-AIDS defining cancers. Multivariable proportional odds logistic and Poisson regression models were used to assess the relationship between baseline SVI (total and themes) and both baseline and longitudinal NCDs (respectively), accounting for clustering and adjusting for age, substance use, gender/HIV risk factor, race/ethnicity, prevalent NCDs, antiretroviral therapy, depression, HIV RNA, hepatitis C, year, CD4 count, time since HIV diagnosis, and body mass index. Continuous variables including SVI were modeled using restricted cubic splines with 3 knots. Results: Among 4440 PWH, median age was 41 years, 59% were men who have sex with men, 21% were cis-gender women, 41% were non-Hispanic Black, and 50% were non-Hispanic white. Median total SVI was 0.6 (IQR: 0.3-0.8) and median follow-up was 2.6 years (IQR: 1.1-5.4). At baseline, 44% had ≥1 NCD and 19% had ≥2 prevalent NCDs. Of 2442 PWH without prevalent NCDs, 32% developed NCDs during follow-up. Of 1916 patients with prevalent NCDs, 41% developed additional NCDs. Lower SVI was associated with lower number of prevalent NCDs (Figure 1a). In separate analyses, SVI socioeconomic status and household composition/disability themes were also associated with prevalent NCD burden (all p<0.05). In longitudinal analyses, there was no significant association between SVI and the risk of incident NCDs (Figure 1b). Conclusion: Neighborhood vulnerability was associated with NCD burden among PWH, even after adjusting for individual characteristics, though confidence intervals included the null for incident NCDs. Relationships between neighborhood-level social determinants of health and NCD comorbidity among PWH warrant further study.

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Dasatinib + Quercetin Drugs Reduced Senescent-Associated Secretory Phenotype (SASP) in PLWH PBMCs Núria Climent , Víctor Casanova, Andrea Rodríguez Agustín, María José Maleno, Cristina Rovira, Josep Mallolas, Juan Ambrosioni, Sonsoles Sánchez-Palomino, José M. Miró, José Alcamí Hospital Clinic of Barcelona, Barcelona, Spain Background: Despite ART virological suppression, PLWH have increased inflammation and age-linked diseases. Research in cellular aging has identified key biomarkers that define senescent cells (SC) which can be eliminated by senolytic drugs. These biomarkers include SA-βGal and mediators such as MCP-1, IL-8 or IL-6 that are principal components of the Senescent Associated Secretory Phenotype (SASP). We previously found that HIV-1 infection increased SC biomarkers such as SA-βGal, Bcl-II and IL-6 in CD4+ T cells. The role of HIV-1 in promoting cellular senescence by SASP and soluble immune checkpoints is not fully understood and could be key to develop new treatments for HIV associated aging comorbidities. We aim to determine SASP mediators, SC linked soluble immune checkpoints (IC) and to know whether Dasatinib plus Quercetin (D+Q) senolytic drugs can influence SASP levels. Methods: PLWH from acute, chronic and advanced infection cohorts before and after a year on ART and a HIV-negative control group (NC) matched by sex and age were included (n=12). D+Q senolytic drugs were added to an ex vivo 3-day culture of PBMC with IL-2 from those cohorts. A set of 34-top SASP and 6 IC mediators were quantified by a customized Luminex in plasma and cell culture supernatants. Unpaired or paired non-parametric T-test and Pearson correlation were performed. Results: SASP (IL-6, IL-8, IL-10, RANTES, GRO-α, TNF-RI/RII, CD30, CD30L, VEGF-A) and IC (PD-1, PD-L1, PD-L2, LAG-3, CTLA-4) mediator levels were higher in advanced and chronic patients than in NC (p<0.05). These mediators were only reduced to NC levels by a year of ART in the acute cohort. IL-6 and SA-βGal in CD4+ T cells levels positively correlated with SASP mediators and IC such as IL-10, MIP-1α, PD-L1, CTLA-4 and LAG-3 (p<0.05). D+Q ex vivo treatment decreased SASP mediators such as MCP-1, IL-8 (Figure), IL-6, IL-10, MIP-1α, IL1-RA, IL-1β, IL-1α, suPAR, PAI-I, tPA, MMP-1, MMP-12, HGF, Leptin, PlGF-1, MCP-4, GM-CSF, TNF-RI, Mip-3α, IL-7 or IL-15 (p<0.05) in non-ART treated PLWH. D+Q drugs in ART PLWH also decreased the above mentioned SASP mediators including MCP-1 and IL-8 (Figure Conclusion: Advanced and chronic PLWH with or without ART showed higher levels of SASP and immune checkpoint mediators. Ex vivo D+Q senolytic treatment decreased the majority of SASP factors analysed, normalizing these levels. These drugs could be useful to reverse cellular senescence, chronic inflammation and aging comorbidities from PLWH.

Poster Abstracts

843

Application of STOPP Criteria in an Urban Cohort of People Aging With HIV Lauren F O'Connor 1 , Jenna Resnik 1 , Sam Simmens 1 , Vinay Bhandaru 1 , La'Marcus Wingate 2 , Debra Benator 1 , Amanda Castel 1 , Anne Monroe 1 , for the DC Cohort Executive Committee 1 George Washington University, Washington, DC, USA, 2 Howard University, Washington, DC, USA Background: The validated Screening Tool of Older People's Prescriptions (STOPP), which identifies potentially inappropriate prescribing (PIP), i.e., treatment for which the potential risk outweighs the potential benefit, may be particularly important for aging people with HIV (PWH) and comorbidities. PIP may exacerbate symptoms and worsen adherence, which is particularly relevant among PWH. Our objectives were to: (1) Apply STOPP to identify PIP among an urban cohort of PWH aged >50 years with >1 comorbidity; (2) Describe

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