Enhancing cardiovascular risk prediction in HIV using novel factors in the REPRIEVE trial - The goal of this proposal is to develop a comprehensive cardiovascular disease (CVD) risk score for people living with HIV (PWH), leveraging the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) to integrate inflammatory and immune biomarkers, imaging, and genetic data. PWH confront an increased burden of CVD thought to be attributable in part to HIV-related inflammation and immune activation. Yet established CVD risk prediction algorithms developed for use in the general population include only traditional CVD risk factors and do not reflect the unique mechanistic factors thought to drive excess CVD risk in PWH. Consequently, established CVD risk prediction algorithms have been hypothesized to underperform in PWH, and several recent studies have demonstrated underestimation of risk. Few CVD risk scores in the current treatment era have been designed specifically for PWH, and none has incorporated biomarkers or genetic data. Through this proposal, we will employ the REPRIEVE cohort to conduct novel analyses to develop comprehensive, accurate HIV-specific CVD risk prediction scores that more fully reflect the complexity of HIV- associated CVD. In Aim 1, we will assess concordance among five established CVD risk prediction scores among all REPRIEVE participants, including a non-laboratory based score and an HIV-specific score, and will assess the association of each score with coronary plaque indices based on coronary computed tomography angiography (CTA). In Aim 2, we will develop new HIV-specific CVD risk prediction scores incorporating clinical CVD and HIV-related factors (Aim 2A), inflammatory and immune biomarkers (Aim 2B), and CTA indices (Aim 2C) to predict major adverse cardiovascular events (MACE). We will specifically assess the performance of the new scores in analyses stratified by sex, race/ethnicity, geographic region, baseline CVD risk score, and receipt of statin in REPRIEVE. In Aim 3, we will investigate whether integration of a novel polygenic risk score developed from the REPRIEVE cohort further enhances accuracy of prediction of CVD events among PWH, assessing interactions between polygenic risk score and sex, race/ethnicity, and geographic region. The proposed work will answer critical questions about how to quantify CVD risk most accurately in PWH, a population that confronts disparities in CVD prevention due to underestimation of risk using established risk scores. Moreover, the studies will have implications for other inflammatory and autoimmune diseases with excess CVD risk. The knowledge gained will impact clinical care paradigms and reduce current inequities in cardiovascular preventive care in the aging HIV population.
