Immediate vs Delayed ART and Long-Term Cardiovascular Outcomes in HIV: START Trial

Overview

This study from the START trial compared cardiovascular disease (CVD) event rates in people with HIV (PHIV) randomized to immediate versus deferred antiretroviral therapy (ART). Over a median follow-up of 9.3 years, no overall difference in CVD event rates was observed between the two groups. A potential benefit of immediate ART was suggested in female participants but not males.

Background

People with HIV have a higher risk of cardiovascular disease compared to those without HIV, influenced by both traditional risk factors and HIV-specific factors such as chronic inflammation and immune activation. While ART reduces HIV viremia and associated risks, some antiretrovirals may have cardiovascular toxicities. The optimal timing of ART initiation to mitigate long-term CVD risk remains unclear, especially in individuals with high CD4+ counts. The START trial randomized ART-naïve adults with CD4+ counts >500 cells/µL to immediate or deferred ART to evaluate clinical outcomes including CVD events.

Data Highlights

Key Findings

• No significant difference in overall CVD event rates between immediate and deferred ART arms (0.17 vs 0.17 per 100 person-years).
• Median time to ART initiation was 7 days in immediate arm versus 2.5 years in deferred arm.
• Among females, immediate ART was associated with a lower risk of CVD events (Hazard Ratio 0.19; 95% CI 0.04–0.86), whereas no benefit was observed in males.
• Traditional CVD risk factors such as smoking (32%), hypertension (19%), and obesity (17% with BMI ≥30) were prevalent in the cohort.
• Findings were consistent across pre-2016 (randomized treatment) and post-2016 (similar ART use) periods.

Clinical Implications

Immediate initiation of ART in PHIV with high CD4+ counts does not appear to reduce long-term cardiovascular events overall, but may confer cardiovascular benefits in female patients. Clinicians should continue to manage traditional cardiovascular risk factors aggressively in PHIV regardless of ART timing. Further research is warranted to clarify sex-specific effects of ART timing on cardiovascular outcomes.

Conclusion

In this large randomized cohort, early ART initiation did not reduce overall CVD events compared to deferred ART, though a potential protective effect in females was observed. These findings highlight the complexity of cardiovascular risk management in PHIV and the need for individualized care.

References

1. INSIGHT START Study Group 2015 -- Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection
2. Triant VA et al. 2018 -- Cardiovascular Disease in HIV-Infected Adults
3. Baker JV et al. 2019 -- HIV and Cardiovascular Disease: Mechanisms and Management