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Publications

Journal Article Epublish

PubMed: 42460401 DOI: 10.1093/ofid/ofag426

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 Infect Dis 13(7):ofag426

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

Affiliations

  • Hospital Universitario 12 de Octubre, imas12 Health Research Institute, Madrid, Spain.
  • CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
  • Hospital Universitario La Paz, IdiPAZ Health Research Institute, Madrid, Spain.
  • Miguel Hernández University, Elche, Spain.
  • Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria de Granada (IBS-Granada), Granada, Spain.
  • Hospital Universitario Infanta Leonor, Madrid, Spain.
  • Hospital Clínico Universitario de Valencia, Valencia, Spain.
  • Hospital Universitario de Canarias, Tenerife, Spain.
  • IDISCAM, Hospital Universitario de Guadalajara, Guadalajara, Spain.
  • Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
  • Hospital de Burgos, Burgos, Spain.
  • Hospital Universitario Puerta de Hierro, Madrid, Spain.
  • Hospital Universitario Son Llàtzer, Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain.
  • Parc Taulí Hospital Universitari, Sabadell, Spain.
  • Institut D'Investigació I Innovació Parc Taulí (I3PT), Sabadell, Spain.
  • Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Hospital Universitario de La Princesa, Madrid, Spain.
  • Álvaro Cunqueiro University Hospital, Vigo, Spain.
  • Hospital Clínico San Cecilio-PTS, Granada, Spain.
  • Hospital General Universitario Reina Sofía, Murcia, Spain.
  • Hospital Universitario Miguel Servet, Zaragoza, Spain.
  • Hospital Clínico San Carlos, Madrid, Spain.
  • Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
  • Universidad Complutense de Madrid, Madrid, Spain.
  • Bellvitge University Hospital, Barcelona, Spain.
  • Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
  • University of Barcelona, Barcelona, Spain.
  • Hospital Universitario de Torrejón, Madrid, Spain.
  • Universidad Francisco de Vitoria, Madrid, Spain.
  • Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  • Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Hospital Universitario de Fuenlabrada, Madrid, Spain.
  • Hospital Universitario San Agustín, Avilés, Spain.
  • Hospital Universitario Mutua Terrassa, Barcelona, Spain.
  • Hospital Universitario de Cabueñes, Gijón, Spain.
  • Hospital Verge de la Cinta, Tortosa, Spain.
  • Hospital Universitario Marqués de Valdecilla, Santander, Spain.
  • Hospital Comarcal de la Vega Baja, Alicante, Spain.
  • Hospital Universitario Fundación Alcorcón, Madrid, Spain.
  • Universidad Rey Juan Carlos, Madrid, Spain.
  • Complexo Hospitalario Universitario de Pontevedra, Instituto de Investigación Sanitaria Galicia Sur, Pontevedra, Spain.
  • Hospital Universitario de Álava, Vitoria-Gasteiz, Spain.
  • Hospital Central de la Defensa Gómez Ulla, Madrid, Spain.
  • Hospital Residencia Sant Camil, Barcelona, Spain.
  • Hospital Universitario Infanta Elena, Madrid, Spain.
  • Hospital Universitario San Jorge, Huesca, Spain.
  • Hospital Universitario de Basurto, Bilbao, Spain.
  • Fundación Para la Investigación e Innovación Biomédica (FIIB) de los Hospitales Universitarios Infanta Leonor (Vallecas) y Sureste (Arganda del Rey), Madrid, Spain.
  • Division of Infectious Diseases, Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Universidad Autónoma de Madrid, Madrid, Spain.

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 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.

MeSH

Nucleosides, Rilpivirine, Therapeutics, Mutation