No Cardiovascular Benefit Seen With Early ART in Low-Risk, ART-Naïve Adults With HIV

In a multinational randomized trial of antiretroviral therapy (ART)-naïve adults with HIV and CD4+ counts above 500 cells/μL, early initiation of ART did not reduce the risk of cardiovascular disease (CVD) events compared with deferred treatment. Researchers presented the study results at the Conference on Retroviruses and Opportunistic Infections 2025 in San Francisco, CA.

Prior studies have demonstrated that people with HIV are at greater risk of CVD compared with the general population, but it remains unclear whether this risk is present in ART-naïve individuals with high CD4+ counts or if delaying ART initiation contributes to increased cardiovascular risk. This trial was designed to evaluate the long-term health impacts of immediate versus deferred ART initiation in otherwise healthy adults with preserved immune function.

Researchers analyzed data from 4684 participants randomized to either immediate ART or deferral until CD4+ counts dropped below 350 cells/μL or AIDS developed. Participants had a median age of 36 years. At baseline, 32% were smokers, 17% had obesity (BMI ≥30 kg/m²), and the median Framingham 10-year CVD risk score was 1.9%. The composite CVD outcome—defined as myocardial infarction, stroke, coronary revascularization, or CVD death—was assessed across three time periods: before 2016 (when ART use differed between arms), after 2016 (when continuous ART was recommended for all), and over the full study duration.

After a median follow-up of 9.3 years, the composite CVD event rate was similar between groups, with no significant difference in the incidence of myocardial infarction, stroke, coronary revascularization, or cardiovascular death. Event rates were nearly identical between treatment groups: 0.18 vs. 0.17 per 100 person-years (PY) in the immediate vs. deferred arms pre-2016, and 0.16 vs. 0.17 per 100 PY post-2016.

Over the entire study period, 71 participants experienced a CVD event—35 in the immediate ART group and 36 in the deferred group—yielding a hazard ratio (HR) of 0.98 (95% CI, 0.61-1.56). Subgroup analysis revealed a lower risk of CVD events in women who initiated ART early (HR, 0.19; 95% CI, 0.04-0.86), but not in men (HR, 1.33; 95% CI, 0.79-2.24), with a significant interaction (P = .014). However, interpretation of this sex-specific finding is limited by the small number of events.

“While immediate ART is known to reduce the risk of many clinical comorbidities and adverse outcomes among PWH, we did not find an effect of early ART initiation for reduction of CVD events among individuals at low CVD risk and moderate to high CD4 counts in the START study,” the authors concluded. “The benefit found among women warrants further evaluation.”

Reference

Dharan NJ, Mistry S, Arenas-Pinto A, et al. Early vs deferred HIV therapy and cardiovascular disease in people with HIV: the START study. Paper presented at: Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Accessed March 24, 2025. https://www.croiconference.org/