Early vs. deferred antiretroviral therapy initiation and long-term cardiovascular disease outcomes in people with HIV: the START study

Background It is unknown whether delayed antiretroviral therapy (ART) initiation worsens CVD outcomes in people with HIV (PHIV). This study compared CVD event rates between PHIV who were randomized to receive immediate vs. deferred ART. Methods ART-naïve adult PHIV with CD4+ counts>500 cells/µL were randomized to immediate vs. deferred ART initiation. Event rates for the main composite CVD outcome (myocardial infarction, coronary artery disease requiring revascularization, stroke and CVD-related death) were estimated for: (i) pre-2016 (treatment arms as designed); (ii) post-1Jan2016 (ART use similar across arms); and (iii) entire study follow up period. Subgroup analyses were performed according to baseline characteristics. Results Among 4,684 participants (median age 36 years, 27% female, 30% Black race), 32% were smokers and 17% had a BMI≥30 kg/m. Comorbidities included hypertension (19%), dyslipidemia (8%), diabetes (3%); 0.8% had a history of CVD. The median time to ART initiation was 2.5 years (interquartile range [IQR] 1.6-3.5 years) in the deferred arm and 7 days (IQR 2-17 days) in the immediate arm. Over the entire study follow up period (median follow-up of 9.3 years), 71 participants (35 immediate, 36 deferred) experienced a CVD event with no difference in CVD event rates between the immediate and deferred arms (0.17 vs. 0.17 per 100 person-years, respectively); these findings were consistent across the pre-2016 and post-1Jan2016 periods. There were 58 CVD events among males (33 immediate; 25 deferred) and 13 among females (2 immediate; 11 deferred). A possible benefit of immediate ART was seen in females but not males (Hazard Ratio=0.19 [95% confidence interval: 0.04-0.86] vs. 1.33 [0.79-2.24]; interaction p-value=0.014), though numbers of events were low. Conclusions Early vs. deferred ART initiation was not associated with reduced CVD events. The potential benefit associated with immediate ART in female participants warrants further evaluation.