Characterizing phenotypes of chronic disease among people aging with HIV in the United States

Despite viral suppression, many people living with HIV (PWH) experience earlier and higher rates of chronic diseases that cluster in complex patterns. These health burdens do not arise in isolation, nor are they evenly distributed across the population. This makes it critical to study the interplay between social factors and HIV- related comorbidities to better understand accelerated aging and guide tailored care. The objective of this R21 application is to apply a syndemic framework to characterize how multiple, co-occurring health conditions cluster and interact under conditions of social and structural adversity, to identify and characterize patterns of disease burden that accelerates aging among groups of PWH. Our central hypothesis is that the varying epidemics of HIV and comorbid diseases are syndemic, in that clusters of diseases observed in populations adversely interact to accelerate aging and are driven by specific social conditions. This hypothesis has been formulated on the basis of a preponderance of literature indicating high rates of comorbid disease in people living with HIV at earlier ages, and that greater social vulnerabilities increase HIV and comorbid disease risk. Our study is innovative in its novel application of a syndemic framework, integration of multilevel biological and social data, and shift in focus from individual conditions to multimorbidity phenotypes, providing actionable pathways for interventions to improve aging outcomes in PWH. We propose conducting a secondary data analysis of the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS) to achieve four specific aims: (1) Characterize comorbid disease phenotypes among PWH and PWOH, (2) Assess whether phenotypes are synergistic in accelerating aging, (3) Determine social and structural drivers of syndemic phenotypes, and (4) Model pathways to identify intervention targets. This R21 application is responsive to the NIA interest in examining the impact of interactions between HIV and comorbid diseases on aging, particularly in low-income areas, as well as interactions among individual-, social- and structural-level factors and their contributions to the well-being of PWH. Our key innovations are the use of novel multivariate statistical approaches to simultaneously model adversely interacting HIV and chronic disease epidemics and their social determinants at both individual and population levels. Understanding multifaceted interventions for aging PWH is essential, as multimorbidity in this population increases healthcare utilization, costs, and caregiver burden. Identifying disease phenotypes will help guide resource allocation and strengthen integrated models of HIV and chronic disease care. Our expected contribution and public health significance includes empirical evidence to inform strategies for interventions and clinical care including social risk screening in HIV care, integrated chronic disease management, and place-based public health strategies designed to interrupt the social processes that drive clustered disease and accelerate aging in PWH. Project Number: 1R21AG099752-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Nicola Bulled | Institution: UNIVERSITY OF CONNECTICUT STORRS, STORRS-MANSFIELD, CT | Award Amount: $450,928 | Activity Code: R21 | Study Section: Population and Public Health Approaches to HIV/AIDS Study Section[PPAH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11411008