RELATIVITY studygroup2026-10-012026-10-012026-07RELATIVITY studygroup 2026, 'Effect of Non-nucleoside Resistance-Associated Mutations on the Effectiveness of Long-Acting Cabotegravir + Rilpivirine Therapy : Insights From the Real-World RELATIVITY Cohort', Open Forum Infectious Diseases, vol. 13, no. 7, ofag426. https://doi.org/10.1093/ofid/ofag4262328-8957PubMedCentral: PMC13371753https://hdl.handle.net/10641/8443Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Antecedentes: El impacto de las mutaciones asociadas a resistencia (RAM) preexistentes a los inhibidores no nucleósidos de la transcriptasa inversa (NNRTI) en la eficacia del cabotegravir (CAB) y la rilpivirina (RPV) de acción prolongada (LA) sigue estando poco definido, especialmente para mutaciones como K103N que no comprometen directamente la susceptibilidad a RPV (RAM a NNRTI no-RPV). Métodos: Este subestudio observacional dentro de la cohorte española RELATIVITY incluyó personas con VIH (PWH) que cambiaron a CAB + RPV LA antes de 2025. Comparamos los resultados virológicos entre aquellos con RAM a NNRTI no-RPV y un grupo de referencia sin RAM a NNRTI/INSTI ni fracaso virológico previo basado en NNRTI (VF). También se analizó un subgrupo adicional con RAM asociadas a RPV. El fracaso virológico confirmado (CVF) se definió como 2 cargas virales consecutivas ≥ 200 copias/mL o 1 ≥500 copias/mL. Resultados: De 1358 participantes, 83 (6,1 %) presentaban RAM a NNRTI no-RPV (47 con K103N) y 1247 sirvieron como grupo de referencia. Tras una mediana de seguimiento de 16,7 meses, las tasas de CVF fueron similares entre el grupo con RAM a NNRTI no-RPV y el grupo de referencia (1,2 % frente a 0,8 %; HR: 1,39; IC 95 %: 0,18–10,84; P = ,755). No se observaron diferencias significativas en los brotes virales (6 % frente a 8,2 %; P = ,481). Cabe destacar que, en el subgrupo de 28 participantes con RAM asociadas a RPV (incluidos 5 con resistencia de alto nivel), no se produjo ningún CVF durante una mediana de 13,5 meses. Conclusiones: En un entorno de la vida real, CAB + RPV LA demostró alta eficacia en PWH con RAM a NNRTI preexistentes que no comprometen la susceptibilidad a RPV, incluida K103N. Aunque no se observaron fracasos en aquellos con RAM asociadas a RPV, estos resultados deben interpretarse con cautela debido al pequeño tamaño de la muestra. [Traducción automática al español; idioma original: inglés.]Background: The impact of pre-existing non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) on the effectiveness of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) remains poorly defined, particularly for mutations like K103N that do not directly compromise RPV susceptibility (non-RPV NNRTI RAMs). Methods: This observational substudy within the Spanish RELATIVITY cohort included people with HIV (PWH) who switched to CAB + RPV LA before 2025. We compared virologic outcomes between those with non-RPV NNRTI RAMs and a reference group without NNRTI/INSTI-RAMs or prior NNRTI-based virologic failure (VF). An additional subgroup with RPV-associated RAMs was also analyzed. Confirmed virologic failure (CVF) was defined as 2 consecutive viral loads ≥ 200 copies/mL or 1 ≥500 copies/mL. Results: Among 1358 participants, 83 (6.1%) harbored non-RPV NNRTI RAMs (47 with K103N) and 1247 served as the reference group. After a median follow-up of 16.7 months, CVF rates were similar between the non-RPV NNRTI RAMs group and the reference group (1.2% vs 0.8%; HR: 1.39; 95% CI: 0.18–10.84; P = .755). No significant differences were observed in viral blips (6% vs 8.2%; P = .481). Notably, in the subgroup of 28 participants with RPV-associated RAMs (including 5 with high-level resistance), no CVFs occurred over a median of 13.5 months. Conclusions: In a real-world setting, CAB + RPV LA demonstrated high effectiveness in PWH with pre-existing NNRTI RAMs that do not compromise RPV susceptibility, including K103N. While no failures were seen in those with RPV-associated RAMs, these results should be interpreted with caution due to the small sample size.11795495enginfo:eu-repo/semantics/openAccessNNRTI resistance-associated mutationslong-Actingreal-worldrilpivirineOncologyInfectious DiseasesSDG 3 - Good Health and Well-beingYes/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.1093/ofid/ofag426https://www.scopus.com/pages/publications/105045150015https://www.scopus.com/pages/publications/105045150015#tab=citedBy