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

Abstract

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.

Keywords: Adherence; Cabotegravir (CAB); Efficacy; HIV treatment; Injectables; Long-acting (LA) HIV therapy; Real-world; Rilpivirine (RPV); Undetectable VL.

Fig. 1

Flowchart of the study design. LA-CAB/RPV  long-acting antiretroviral therapy with cabotegravir and rilpivirine (created in BioRender, Dannenberg, C. (2025) https://BioRender.com/7p08hou)

Fig. 2

Individual LA-CAB/RPV therapy duration in injection-experienced individuals (cohort (b)). The light grey background highlights the observation period. Yellow bars represent therapy duration during prior clinical trials, while orange bars indicate continuation of treatment to routine clinical care within the observation period. The transition from clinical trial participation to routine care occurred after the end of the previous study, not at the beginning of the observation period. Participants ID-HH 7, ID-HH89, and ID-HH 103 were lost to follow-up owing to relocation (created in BioRender, Dannenberg, C. (2025) https://BioRender.com/g4dobmp)

Fig. 3

Adherence to the time schedule among in-label participants. Injection timing adherence in cohort (a) and cohort (b) across 1690 administered injections, shown in dark grey box plots. The grey-shaded area represents the tolerance window (± 7 days from the scheduled injection date); injections to the left were administered early, while those to the right were delayed. The purple box plots represent the percentage of viral load increases corresponding to each adherence category. Percentages were calculated on the basis of the number of injections within each adherence group for which a blood draw was available; n number, VL viral load (created in BioRender, Dannenberg, C. (2025) https://BioRender.com/fzwg2n9)

Fig. 4

a Adherence and virological outcomes in injection-naïve individuals (cohort a) (created in BioRender, Dannenberg, C. (2025) https://BioRender.com/eawxe5w); b Adherence and virological outcomes in injection-experienced individuals (cohort b). Adherence and virological outcomes of LA-CAB/RPV treatment over the timeline (x-axis) for each individual (y-axis). Adherence is visualized by length of the intervals between injections, represented as boxes along each participant’s timeline. Delays beyond the scheduled injection dates are annotated with the corresponding number of days overdue. To ensure visibility of initial VL data, the width of the first interval block was standardized. Virological outcomes are visualized by different colors: light green: undetectable VL (< 13.2 copies/mL); green: VL < 50 copies/mL; red: VL 51–200 copies/mL; and dark red: VL > 200 copies/mL. Follow-up visits at 12–15 months, 24–27 months, and 36–39 months are marked by vertical lines. *Discontinuations, CVF, LTFU, and relocations were annotated; n number, CVF confirmed virological failure, LA-CAB/RPV long-acting antiretroviral therapy with cabotegravir and rilpivirine, LTFU lost to follow-ups, VL viral load (created in BioRender, Dannenberg, C. (2025) https://BioRender.com/y5txl4d)

Fig. 5

Virological outcomes at follow-up time windows among in-label participants. Long-term virological outcomes of all available in-label participants at defined follow-up time windows, stratified by HIV-1 VL < 50 copies/mL, VL ≥ 50 copies/mL, and undetectable VL (< 13.2 copies/mL). The number of participants varies due to loss to follow-up (e.g., discontinuation, relocation, or other reasons) or/and the end of the observation period. In cohort (a), data were available up to the 36–39-month follow-up window. As the observation period ended after 44 months, no data from the cohort (a) were available for the 48–51-month window or beyond. In cohort (b), injection-experienced participants transitioned to routine care at different time points. The earliest transitions occurred after 32 months of LA-CAB/RPV therapy and involved two individuals. By the 48–51-month follow-up, n = 9 participants had entered the observational phase, increasing to n = 13 individuals at 72–75 months. Thereafter, participant numbers declined due to the end of the observation period. Notably, n = 3 individuals remained on LA-CAB/RPV therapy for a full 10 years and consistently maintained viral loads < 50 copies/mL. n number, HIV-1 human immunodeficiency virus type 1, LA-CAB/RPV long-acting antiretroviral therapy with cabotegravir and rilpivirine, VL viral load (created in BioRender, Dannenberg, C. (2025) https://BioRender.com/e53rcfh)