Long-acting CAB + RPV: safety, efficacy, and discontinuation risks in ODOACRE cohort

Purpose: Real-world data on long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) durability, safety, and discontinuation risk are limited. We present findings from a large multicenter cohort, focusing ondiscontinuation rates and metabolic/immunologic changes over time. Method: All people with HIV (PWH) initiating LA-CAB/ RPV in six Italian centers were included. Data ondemographics, clinical information and laboratory parameters at baseline and after 12 and 24 months were collected. The primary endpoint was cumulative probability of all-cause treatment discontinuation (TD). Kaplan-Meier estimates were used to assess TD probability, and Cox models to assess associated risk factors. Results: Three hundred thirty-six PWH were included, mostly males (79.3%), with a mean age of 48.3 years (main features in Table 1). The total follow-up was 8,783 person-months. Overall, 43 PWH discontinued treatment (Figure 1). The cumulative probability of TD was 10.0% (95% CI: 7.4%–13.5%) and 11.3% (95% CI: 8.5%–14.9%) at 12 and 24 months, respectively. Discontinuation due to virological failure (VF) was 1.9% at both 12 and 24 months. Injection site reactions (ISRs) led to discontinuation in 3.5% of cases, while 2.2% of people stopped treatment based on personal decision by 12 months, rising to 2.9% at 24 months (Figure 2). Cox analysis did not identify any significant association between baseline variables and overall discontinuation or VF. However, depression was significantly associated with personal-driven decision to stop treatment (HR: 3.63, 95%CI: 1.03–12.88). We observed a CD4/CD8 ratio increase (Table 2) and an improvement of renal function, especially in those previously treated with bictegravir or dolutegravir. HDL increased modestly, while LDL, total cholesterol, triglycerides, and liver function tests did not change over 12 months (Table 2). Conclusions: In this real-life cohort, LA-CAB+RPV demonstrated sustained virologic effectiveness and tolerability. Appropriate user selection remains critical to optimize durability and outcomes of such therapeutic approach.