Determinants of long-acting cabotegravir plus rilpivirine discontinuation in real-world HIV care: insights from the relativity cohort.

OBJECTIVES

To evaluate real-world persistence with long-acting cabotegravir plus rilpivirine (CAB+RPV LA) in a nationwide cohort of virologically suppressed adults, describe the main clinical and structural reasons for discontinuation, and identify predictors of early interruption in routine practice.

DESIGN

Ambispective, multicenter cohort study assessing the durability, safety, adherence, and virological outcomes of CAB+RPV LA implementation across 58 Spanish healthcare settings.

METHODS

Adults initiating CAB+RPV LA therapy were enrolled using standardized electronic tools. Baseline demographics, comorbidities, HIV and virological variables, and injection timing were recorded. Permanent discontinuations were attributed to systemic adverse events, injection-site reactions, virological failure (VF), or nonclinical causes. The virological endpoints were aligned, although not identical, to the CONSENSUS-LAI criteria. Kaplan-Meier curves and multivariate Cox models were used to identify the independent predictors.

RESULTS

Among 3146 virologically suppressed participants, 199 (6.3%) permanently discontinued therapy over a median 13.8-month follow-up. Discontinuation was more frequent among women (21.6 vs. 14.4%; P = 0.007), foreign-born individuals (42.9 vs. 29.5%; P  < 0.001), those with a higher BMI, and those with shorter prior suppression periods. injection-site reaction- and systemic adverse event-related discontinuations were rare (1.2 and 0.7%, respectively), whereas structural reasons accounted for 3.5%. VF occurred in 20 participants (0.6%). Adjusted analyses showed that age ≥70 years [hazard ratio (HR) 5.41; 95% confidence interval (CI) 1.91-15.32] and foreign nationality (HR 2.06; 95% CI 1.48-2.86) independently increased discontinuation risk, whereas male sex (HR 0.65; 95% CI 0.44-0.96) and longer suppression (HR/day 0.99; P  = 0.036) were protective.

CONCLUSIONS

In this large national cohort, CAB+RPV LA demonstrated strong persistence, excellent tolerability, and very low rates of VF. Discontinuations were mainly structural, highlighting the need to reinforce continuity-of-care pathways and system-level support for optimal CAB+RPV LA scale-up.