Long-term Effectiveness, Treatment Persistence, and Timing of Virological Failure With Long-Acting Cabotegravir Plus Rilpivirine in Real-World HIV Care: RELATIVITY Cohort.

BACKGROUND

Long-acting injectable cabotegravir plus rilpivirine (CAB + RPV LA) is an established maintenance option for virologically suppressed people with human immunodeficiency virus-1 (HIV-1), but long-term real-world persistence and virological failure (VF) data remain limited.

METHODS

RELATIVITY is an ongoing nationwide ambispective multicenter cohort of adults with HIV who switched from suppressive oral antiretroviral therapy to CAB + RPV LA in routine care in Spain. Data through 1 March 2026 were analyzed. The outcomes were virological suppression, treatment persistence, protocol-defined VF, and time to discontinuation-related events. Virological failure was defined as 2 consecutive HIV-1 RNA values ≥200 copies/mL or 1 value ≥500 copies/mL prompting discontinuation.

RESULTS

Among 3349 participants, 3343 had valid follow-up dates; the median follow-up was 25.1 months (19.3-30.8). Virological suppression was documented in 3197/3349 (95.5%) overall and 3197/3309 (96.6%) with an evaluable closest viral load; 40 (1.2%) lacked an evaluable value. Injection adherence was ≥90% in 3257/3280 (99.3%) evaluable participants. Overall, 2979/3349 (89.0%) remained on CAB + RPV LA. Virological failure occurred in 28/3349 (0.8%); 20/28 (71.4%) occurred within the first 12 months after switching. Emergent integrase strand transfer inhibitor and/or nonnucleoside reverse transcriptase inhibitor resistance was detected in 19/28 VF cases, and 24/28 achieved virological suppression after switching to oral therapy. Treatment-limiting injection-site reactions and systemic adverse events occurred in 2.4% and 1.6%, respectively.

CONCLUSIONS

Long-acting injectable cabotegravir plus rilpivirine showed high virological suppression and persistence beyond 2 years in routine care. Virological failure was uncommon and clustered mainly within 12 months, supporting early virological monitoring and prompt resistance-guided management.