Analytical description of adverse events with long-acting injectable cabotegravir and rilpivirine in people living with HIV: a large multicentre prospective observational cohort study (SCOLTA)

INTRODUCTION: Long-acting injectable cabotegravir plus rilpivirine (LA CAB+RPV) is a highly effective, well-tolerated antiretroviral regimen, but real-world adverse event (AE) data remain limited. We characterised the type and frequency of AEs associated with LA CAB+RPV in people with HIV in routine clinical practice. METHODS: This multicentre, prospective, observational study (SCOLTA project, Italy) enrolled people with HIV initiating LA CAB+RPV. Clinical characteristics, AEs and discontinuations were systematically collected. A centre-level survey assessed AE management and prevention practices. RESULTS: In our cohort 598 people with HIV were enrolled across 25 centres. Forty-two participants (7%) experienced overall 51 AEs, of which 37 (88%) led to discontinuation of LA injectable therapy. Injection site reactions (ISRs) were the most frequently reported AEs (29.4%). Central nervous system (CNS)-related AEs accounted for 7.8% of events and resulted in treatment discontinuation in 75% of cases. In multivariable analysis, unknown HIV acquisition mode was independently associated with an increased risk of AEs. Age ≥50 years showed a consistent trend across all models and was the only significant independent predictor in sensitivity analyses restricted to people with HIV with known HIV acquisition mode. Among the 23 centres responding to the survey, 15 (65.2%) reported a reduction in injection-related events following specific training of staff administering LA CAB+RPV. CONCLUSIONS: LA CAB+RPV showed a lower AE rate than pivotal trials, despite more AE-related discontinuations. CNS-related AEs were uncommon, supporting good tolerability, but led to discontinuation when they occurred. Older age was independently associated with increased AE risk.