Effect of Non-nucleoside Resistance-Associated Mutations on the Effectiveness of Long-Acting Cabotegravir + Rilpivirine Therapy: Insights From the Real-World RELATIVITY Cohort.

Authors

David Rial-Crestelo, Jara Llenas-García, Carmen Hidalgo-Tenorio, Jesús Troya García, María José Galindo Puerto, María Remedios Alemán Valls, Miguel Torralba González de Suso, Luis Buzón, Alberto Díaz de Santiago, Adrián Rodríguez, Sonia Calzado Isbert, María Aguilera García, Luis Enrique Morano Amado, David Vinuesa García, Enrique Bernal Morell, Rosa María Martínez Álvarez, Noemí Cabello-Clotet, Analuz Fernández, María Del Carmen Montero Hernández, Cristina Díez Romero, Ruth Calderón Hernaiz, Desiree Pérez Martínez, Laura Gisbert Pérez, Víctor Arenas García, Cristina Escrich, María Carmen Fariñas Álvarez, Ana Lucas Dato, Juan Emilio Losa García, Hadrián Pernas Pardavila, Juan Carlos Gainzarain, Miriam Estébanez, Patricia Barragán Gallo, Marta Clavero Olmos, Miguel Vicente Egido Murciano, Oscar Luis Ferrero Benéitez, Roberto Pedrero-Tomé, Alfonso Cabello-Úbeda, Luz Martín-Carbonero, RELATIVITY studygroup

Published in

Open forum infectious diseases. Volume 13. Issue 7. Pages ofag426. Epub Jul 07, 2026.

Abstract

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).
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.
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.
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.

PMID:
42460401
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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