Immune Trajectories After Switch to Long-Acting Cabotegravir Plus Rilpivirine in the RELATIVITY Cohort
Jesús Troya, Noemí Cabello-Clotet, José Ignacio Bernardino, María José Galindo, Rosa María Martínez, Juan Martín, María Remedios Alemán, Miguel Torralba, Francisco Fanjul, María Carmen Fariñas, Adrián Rodríguez, María José Crusells, Sonia Calzado, Javier Pérez-Serrano, Carmen Hidalgo-Tenorio, Luis Enrique Morano, David Vinuesa, Enrique Bernal-Morell, Inmaculada Poquet-Catalá, Hadrián Pernas-Pardavila, Juan Tiraboschi, Diana Corps, María Jesús Vivancos, Luis Buzón-Martín, , Ana Cristina Antolí Royo, Carmen Grande Sáez, María Ángeles Garcinuño Jiménez, Ana Carrero Gras, Eva María Ferreira Pasos, Hadrian Pernas Pardavila, Mercedes González, Nuria Vázquez Temprano, Miriam Estébanez, Tatiana Mata-Forte, Ana Muñoz Gómez, Claudia Dorta Hernández, José Reynaldo Homen Fernández, Juncal Pérez-Somarriba Moreno, Maravillas Carralón, María José Núñez Orantos, María Nieves Sanz Pérez, Noemí Cabello-Clotet, Philip Erick Wickman Jorgensen, Susana Olmedo Hernández, Teresa Martínez Burgoa, Valeria Cabral Sousa, Vicente Estrada Pérez, Virginia Víctor Palomares, Ana Ferrer Ribera, Andreu Belmonte, Ángela Pradilla Dieste, Carolina Pinto, María José Galindo Puerto, Rosa Oltra Sempere, Sandra Pérez Gómez, Álvaro Cecilio, Isabel Sanjoaquín Conde, María José Crusells Canales, Pilar Jiménez Marcen, Ana Lucas Dato, Belén Martínez López, Inmaculada González Cuello, Jara Llenas García, María García López;, Carolina Navarro, Luis Buzón Martín, María Fernández;, Amparo Exojo Morales, Carlos de Andrés David, Inmaculada Poquet Catalá, Karenina Antelo Cuéllar, 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 García Torras, Marta Milián Sanz, Ana Isabel Lérida Urteaga, Antonia Pérez Barja, Javier López-Nieto, Magdalena Muelas Fernández, Beatriz de la Calle, Ángela Botella Zaragoza, Félix Gutiérrez Rodero, Javier García Abellán, Mar Masiá, Paula Mascarell Arlandis, Sergio Padilla Urrea, Chiara Fanciulli, Cristina Díez Romero, Francisco Tejerina Picado, Juan Carlos de Quirós López Bernaldo, Leire Pérez Latorre, María Teresa Aldamiz-Echevarría Lois, Antonio Jesús Sánchez Guirao, Ángeles Muñoz Pérez, Antonia Alcaraz García, Cristina Tomás Jiménez, Elena Guijarro Westermeyer, Enrique Bernal Morell, Eva García Villalba, Joaquín Bravo Urbieta, María Dolores Hernández Lorente, Rodrigo Martínez Rodríguez, Román González Hipólito, Noemí Ramos Vicente, Patricia Barragán Gallo, Alberto Juárez Toquero, Beatriz Valentín Casado, Jesica Abadía Otero, Julia Gómez Barquero, Pablo Bachiller Luque, Yolanda Arranz García, Adriana Pinto, David Rial, Federico Pulido, Juan Martín, Laura Bermejo Plaza, María de Lagarde, María Teresa López Caballero, Mireia Santacreu, Otilia Bisbal, Rafael Rubio, Roser Navarro, Victoria Macheño del Real, Celia Miralles Álvarez, Guillermo Pousada, Henar de las Heras Miralles, Luis Enrique Morano Amado, Víctor Asensi, Laura Guio Carrión, Mikel del Álamo, Ester Sáez de Adana Arroniz, Juan Carlos Gainzarain Arana, Ana Vegas Serrano, Juan Emilio Losa García, María Velasco Arribas, Maite Ganchegui Aguirre, Miriam López Martínez, Óscar Luis Ferrero Benítez, Alicia Sedo Mor, Analuz Fernández, Juan Tiraboschi, Josefa Soler González, Víctor Arenas García, Lucía Romero, Nereyda Tosco García, Remedios Alemán Valls, Guillermo Soria Fernández-Llamazares, Juan Víctor San Martín López, Ruth Calderón Hernáiz, Alberto Delgado Fernández, Lorenzo Sánchez, Miguel Torralba González de Suso, Alberto Romero Palacios, María Antonia Sepúlveda, Alejandra Gimeno García, Alejandro David Bendala Estrada, Carmen Montero Hernández, Diana Corps Fernández, Jose Carlos Escribano, María del Mar García Navarro, Marouane Menchi Elanzi, Ana Cerezales Calviño, Bárbara Alonso Moreno, José Fernando Lluch Perales, Alfonso Cabello, Miguel Górgolas Hernández-Mora, María Rubio Olivera, Marta Clavero Olmos, Belén Escribano Losada, Guillermo Cuevas, Jesús Troya García, Mariano Matarranz, Pablo Ryan, Sandra Rodríguez Perut, Alejandro de Gea, Ana Belén Delgado Hierro, Carmen Busca, Jose Ignacio Bernardino, Juan González García, Luz Martín Carbonero, María del Mar Arcos Rueda, María Luisa Montes, Rafael Micán, Rocío Montejano, Andoni Casen Gil, Ignacio de los Santos, María Aguilera García, Aitziber Illaro Uranga, Carlos Armiñanzas Castillo, Claudia González-Rico, Francisco Arnaiz de las Revillas Almajano, Manuel Gutiérrez Cuadra, María Carmen Fariñas Álvarez, Noelia Ruiz-Alonso, Paula Runza, Raúl Parra-Fariñas, Ángela Forcén Vicente de Vera, María Aranzazú Caudevilla Martínez, Rosa María Martínez Álvarez, Ruth Caballero Asensio, David Dalmau Juanola, Laura Gisbert Pérez, Mireia Cairó Llobell, Roser Font Canals, Xavier Martínez Lacsa, José Sanz, Alberto Díaz de Santiago, Ana Fernández Cruz, Sara de la Fuente Moral, Ana Moreno, Daniel de las Heras Gómez, María Jesús Pérez Elías, María Jesús Vivancos Gallego, Mario Pons Guillén, Desiré Pérez Martínez, María Elisa Pino Díaz, Miguel Alberto de Zárraga Fernández, Miguel Vicente Egido Murciano, Teresa Omiste Sanvicente, Adrián Ferré, Antoni Campins, Francisco Fanjul, Luisa Martín Pena, Melchor Riera, Adrián Rodríguez, Patricia Sorní Moreno, Carmen Hidalgo Tenorio, Sergio Sequera Arquelladas, Cristina Escrich, María del Carmen Navarro, David VinuesaAbstract
Background
Immune and virological trajectories after switching to long-acting cabotegravir plus rilpivirine (CAB+RPV LA) remain incompletely characterized in routine care settings.
Methods
We analyzed virologically suppressed adults switching to CAB+RPV LA in the Spanish multicenter RELATIVITY cohort. Paired CD4+, CD8+, and CD4/CD8 measurements were assessed at approximately 12 and 24 months and at the last available immune assessment. Analyses used a 1.0 ratio threshold and incorporated longitudinal HIV-1 RNA, recorded geographic origin, pre-switch suppression duration, and immediate pre-switch antiretroviral therapy.
Results
Among 3349 participants, the last paired-ratio assessment (n = 2929) occurred at a median of 22 months (IQR, 16–27). Median changes were −7 cells/mm3 (IQR, −138 to +117; n = 2992) for CD4+ T-cell count, −60 cells/mm3 (IQR, −214 to +75; n = 2941; P < .001) for CD8+ T-cell count, and +0.07 (IQR, −0.05 to +0.20; n = 2929; P < .001) for the CD4/CD8 ratio. Baseline CD4/CD8 <1.0 was independently associated with greater ratio increase (adjusted beta, +0.060; 95% CI, +.030 to +.090; P < .001). Longer pre-switch suppression and any post-switch HIV-1 RNA ≥50 copies/mL were associated with smaller ratio increases. Adjudicated virological failure occurred in 28/3349 (0.8%). Findings persisted among participants with all recorded post-switch HIV-1 RNA values <50 copies/mL and after excluding protocol-defined virological failure.
Conclusions
During effective CAB+RPV LA maintenance, CD4+ T-cell counts showed no meaningful change, while a modest decline in CD8+ T-cell counts was accompanied by a small CD4/CD8 ratio increase. These descriptive changes are compatible with continued immune evolution during sustained suppression and do not establish a CAB+RPV-specific effect or justify additional routine T-cell-subset monitoring.