“Effect of Non-Nucleoside Resistance Associated Mutations on the Effectiveness of Long-Acting Cabotegravir + Rilpivirine Therapy: Insights from the Real-World RELATIVITY Cohort”

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ID: 319699
2026
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Abstract
Abstract 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 two consecutive viral loads ≥ 200 copies/mL or one ≥500 copies/mL. Results Among 1,358 participants, 83 (6.1%) harbored non-RPV NNRTI RAMs (47 with K103N) and 1,247 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.
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Authors David Rial‐Crestelo, Jara Llenas‐García, Carmen Hidalgo‐Tenorio, Jesús Troya, María José Galindo Puerto, María Remedios Alemán Valls, Miguel Torralba, Luís Buzón, Alberto Díaz de Santiago, A. Carolina Rodríguez, Sònia Calzado, María Aguilera García, Luís Morano, David Vinuesa García, Enrique Bernal Morell, Rosa Maria Martínez Álvarez, Noemí Cabello‐Clotet, Analuz Fernández, M Montero-Hernández, Cristina Díez Romero, Ruth Calderón Hernáiz, Desirée Pérez Martínez, Laura Gisbert Pérez, Víctor Arenas García, Cristina Escrich, M Alvarez, 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, Luz Martín‐Carbonero, Relativity studygroup, Ana Cristina Antolí Royo, Carmen Grande Sáez, Maria Ángeles Garcinuño Jiménez, Ana Carrero Gras, Eva María Ferreira Pasos, Pablo Bachiller Luque, Mercedes González, Nuria Vazquez Temprano, Ana Muñoz Gómez, Jose Reynaldo Homen Fernandez, Juncal Pérez-Somarriba Moreno, Maravillas Carralon, María José Núñez Orantos, M Guadalupe Perez, N. Cabello Clotet, Susana Olmedo Hernández, Valeria Cabral Sousa, Vicente Estrada, Virginia Víctor Palomares, Ana Ferrer Ribera, Andreu Belmonte, Carolina Pinto, R Sempere, Sandra Pérez Gómez, Álvaro Cecilio, Isabel Sanjoaquín Conde, Maria Jose Crusells Canales, Pilar Jimenez Marcen, Belén Martínez López, Inmaculada González Cuello, Jara Llenas-García, María García López, Carolina Navarro, María Fernandes, A. Morales, Carlos de Andrés David, Inmaculada Poquet Catalá, Karenina Antelo Cuellar, Laia Navarro Peiró, María Josefa de la Asunción Villaverde, Silvia Lope Bolumar, Alba León Barbosa, Esther Nogales Nieves, Eva García Alcalde, Juan José Corte García, Lucía Alonso Alonso, María Vanessa López Peláez, Sara Jaber Carballo, Albert Gómez Lozano, Sara Garcia Torras, Marta Milián Sanz, Ana Isabel Lérida Urteaga, Antonia Pérez Barja, Javier López-Nieto Sempere, M Isabel Fernandez, Beatriz de la Calle
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Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag426
URL
https://doi.org/10.1093/ofid/ofag426
Keywords Keywords not found

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