Characterizing and predicting comorbidity cascade among men and women with and without HIV by harnessing data from MWCCS and electronic medical records

ABSTRACT Older persons with HIV (PWH) face a higher risk, greater burden, and faster progression of age-related comorbidities, including cardiovascular diseases, metabolic disorders, renal dysfunction, obstructive lung disease, liver cirrhosis, and cancers, compared to those without HIV. These comorbidities lead to polypharmacy, adverse outcomes, and premature death. Understanding the cascade of comorbidity events and the natural history of these conditions among PWH is essential to guide secondary prevention and early interventions. The MACS/WIHS Combined Cohort Study (MWCCS) has significantly advanced HIV care by providing insights into HIV transmission, risk factors, and AIDS and non-AIDS outcomes among PWH using an interval cohort design. We propose to enrich this data source by establishing an electronic health record registry nested within the MWCCS (Aim 1) to study comorbidity burden and cascade among people with and without HIV. Furthermore, we will leverage existing cohort-wide biobehavioral data and the newly linked EHR data to develop predictive models of the comorbidity cascade among people with and without HIV (Aim 2). The proposed R21 work directly responds to PAR-24-092 by studying the aging and comorbidities of HIV using multidisciplinary approaches. Advanced clinical informatics tools, statistical learning models, and leveraging existing MWCCS infrastructure and biobehavioral measurements will shed light on aging and comorbidities in PWH. It will identify high-risk individuals prone to high comorbidity burden, thus paving the way to eventually be able to provide guidance on clinical decision making and care. Notably, this transformative initiative will serve as a pilot platform, leveraging MWCCS infrastructure, real-time EHR data, and existing cohort biomarkers. The data pipeline developed through this project will provide a scalable foundation for expansion to other MWCCS study sites in the near future, significantly broadening the scope and impact of ongoing research in HIV, aging, and comorbidity.