Background
People with HIV (PWH) face an elevated risk of cardiovascular diseases, including heart failure (HF), due to a combination of traditional risk factors and HIV-related mechanisms such as chronic inflammation and immune dysregulation. Despite advances in antiretroviral therapy (ART), the incidence and predictors of HF in PWH remain inadequately characterized. The REPRIEVE trial aimed to quantify HF risk in a global cohort of PWH with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk.
Study Design
The REPRIEVE trial enrolled 7,769 participants from five global regions, with a median age of 50 years and 31% female representation. The study assessed HF incidence over a median follow-up of 5.6 years, using adjudicated HF hospitalizations and adverse events identified via standardized Medical Dictionary for Regulatory Activities queries. Key predictors included demographic, HIV-specific, and traditional cardiovascular risk factors.
Key Findings
HF incidence was 1.65 events per 1,000 person-years (95% CI: 1.30–2.09). Higher HF rates were observed in:
Demographic Groups
– Women (compared to men).
– Black participants in high-income regions.
– Participants in sub-Saharan Africa.
Clinical Factors
– Preexisting hypertension and obesity.
– Notably, HIV-specific markers (current/nadir CD4+ T-cell count, HIV-1 RNA level) were not associated with HF risk.
Risk Prediction
The median Predicting Risk of Cardiovascular Disease Events (PCE) HF score was 1.66% (Q1–Q3: 1.01–2.62). The observed HF events (n=67) closely matched the expected number (n=73) based on PCE HF scores.
Expert Commentary
These findings underscore the predominant role of traditional cardiovascular risk factors, rather than HIV-specific markers, in HF risk among PWH. The REPRIEVE trial highlights the need for targeted interventions in high-risk subgroups, particularly women and Black individuals in high-income settings. Limitations include the exclusion of PWH with high baseline ASCVD risk and potential underrepresentation of certain regions.
Conclusion
The REPRIEVE trial provides critical insights into HF risk stratification in PWH, emphasizing the importance of managing traditional risk factors. Future research should explore tailored preventive strategies and the mechanistic interplay between HIV and cardiovascular pathophysiology.
Funding and Registration
The study was funded by the National Institutes of Health and registered on ClinicalTrials.gov (NCT02344290).
References
Bloomfield GS et al. Heart Failure Risk and Events in People With HIV: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Circ Heart Fail. 2025;19(4):e013382.