Long-Term Real-World Use of Cabotegravir/Rilpivirine: Adherence and Virological Efficacy over a 44-Month Observation Period.

Introduction: Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) offers an effective alternative to daily oral antiretroviral therapy (ART) for people living with human immunodeficiency virus (PLWH), especially those with adherence challenges. Despite increasing use of LA-CAB/RPV, long-term real-world data on durability, adherence, and virological outcomes remain limited to 2 years. This study provides detailed longitudinal data at the individual PLWH level, assessing adherence, safety, and efficacy over a period of up to 10 years.

Methods: All PLWH receiving LA-CAB/RPV at the University Medical Center Hamburg-Eppendorf between 2021 and 2025 were analyzed over 44 months, including injection-naïve individuals and former registration trial participants. Clinical, laboratory, immunological, and virological data were reviewed.

Results: In total, 102 PLWH received ≥ 2 LA-CAB/RPV injections: (a) 77 injection-naïve and (b) 20 injection-experienced participants from clinical trials; and 5 off-label treated participants who were analyzed separately. Among participants treated in-label, 84% (1417/1690) of injections were administered on time. However, 82% of all participants (80/97) experienced ≥ 1 delay, with 96% (77/80) of delays limited to 8-14 days. Virological suppression (VL < 50 copies/mL) was achieved by 97% throughout the observation period (94/97). In total, 14% (14/97), all of cohort (a), discontinued injection therapy and switched back to oral ART. Injection site reactions were reported by 64%, while mild systemic side effects occurred in 41% at some point, most commonly neuropsychiatric symptoms in those with a history of depression. One confirmed virological failure (CVF) occurred after 40 months in cohort (a); two CVFs were observed in the small off-label-treated subgroup.

Conclusions: This real-world study, with a 44-month observation period and follow-up of up to 10 years on LA-CAB/RPV, confirms its long-term efficacy and safety, supporting its durability as a maintenance option for PLWH, even with occasional delays and slightly lower adherence than seen in clinical trials, and additionally underscores the importance of individualized care and structured monitoring in real-world settings.