Comprehensive Cardiovascular Risk Profiling in People Living with HIV: Insights from the Japanese Adverse Drug Event Report Database

Antiretroviral therapy (ART) has dramatically improved outcomes for people living with HIV (PLWH), yet concerns about cardiovascular disease (CVD) remain, especially in aging populations. In this study, we aimed to evaluate the association between ART regimens and CVD events in Japan using a nationwide pharmacovigilance database. We retrospectively analyzed reports from the Japanese Adverse Drug Event Report Database spanning April 2004 to September 2024. After removing duplicates and records with key missing data, 796,402 reports (Population A) were used for signal detection based on the reporting odds ratio (ROR) and information component (IC). A refined subset (Population B; 2,721 reports) underwent logistic regression to identify risk factors for major adverse cardiovascular events (MACE) and total cardiovascular events (MACE plus angina). ART regimen classes (e.g., integrase strand transfer inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors) and backbone therapies [e.g., abacavir (ABC)/lamivudine] were included in the analysis. Signal detection revealed significant ABC signals in both ROR and IC analyses for MACE and total CVD events. In logistic regression, advanced age (≥70 years), ABC-containing regimens, and diabetes emerged as independent risk factors for MACE and total CVD events. Dyslipidemia and hypertension were not significant in the adjusted models. Our findings underscore a potentially heightened cardiovascular risk associated with ABC, particularly in older PLWH or those with diabetes. These results highlight the need to consider individual CVD risk profiles when selecting ART regimens and reinforce the importance of ongoing pharmacovigilance to guide safer, more personalized treatment strategies worldwide.