A prospective assessment of the efficacy and durability of long-acting cabotegravir and rilpivirine in individuals with HIV in Spain (RELATIVITY study).

Background: Daily oral antiretroviral therapy (ART) has transformed HIV into a chronic, manageable condition, but it still poses psychological, logistical, and biological challenges. Long-acting injectable (LAI) cabotegravir plus rilpivirine provides an alternative for virologically suppressed individuals, reducing treatment fatigue, stigma, and daily dosing. While clinical trials have demonstrated efficacy and safety, real-world data remain limited. We assessed the effectiveness and safety of LAI cabotegravir plus rilpivirine in Spain.

Methods: RELATIVITY is a 5-year, multicentre, ambispective, non-controlled cohort study. The primary endpoint was treatment effectiveness, defined as the proportion of patients discontinuing LAI therapy for any reason, including loss of virological suppression (HIV-RNA >50 copies/mL) during follow-up, regardless of formal failure criteria.

Results: This interim analysis (cut-off: March 1, 2025) included 3203 patients from 58 Spanish hospitals; 57 were excluded due to detectable viral load at switch, leaving 3146 participants. Most were men (84.6%), with a median age of 45 years. Median time on ART before switching was 9.0 (5.0-15.0) years, and duration of viral suppression was 84.0 (36.0-132.0) months. Prior integrase inhibitor-based regimens were reported in 77.1%. Virological suppression was maintained in ≥96% through 23 months of follow-up. Overall, 6.4% (n = 199) discontinued, most frequently for injection-site reactions (n = 45), systemic adverse events (n = 29), or virological failure (n = 20).

Conclusions: Interim results from the RELATIVITY cohort confirm high effectiveness and safety of LAI cabotegravir plus rilpivirine in Spanish clinical practice, consistent with randomized trial outcomes and real-world data. An extended follow-up will provide further insights.