Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events

Authors: Javier Martínez‐Sanz, Jorge Díaz-Álvarez, Marta Rosas Cancio-Suárez, Raquel Ron, José Antonio Iribarren, Enrique Bernal, Félix Gutiérrez, Andrés Ruiz Sancho, Noemí Cabello, Julián Olalla, Santiago Moreno, Sergio Serrano‐Villar, Inmaculada Jarrín, David Dalmau, Ma Luisa Masó Navarro, Maria Gonzalez, Féderico García, Eva Poveda, José Antonio Iribarren, Félix Gutiérrez, Rafael Rubio, Francesc Vidal, Juan Berenguer, Juan González, María Ángeles Muñoz‐Fernández, Inmaculada Jarrín, Cristina Moreno, Marta Rava, Rebeca Izquierdo, María Ángeles Muñoz‐Fernández, Elba Mauleón, Joaquín Portilla, Irene Portilla, Esperanza Merino, Gema García, Iván Agea, José Sánchez–Payá, Juan Carlos Rodrı́guez, Livia Giner, Sergio Reus, Vicente Boix, Diego Torrús, Verónica Pérez, Julia Portilla, Juan Luís Gómez, Jehovana Hernández, Ana López Lirola, Dácil García, Felícitas Díaz-Flores, M. Mar Alonso, Ricardo Pelazas, M. Remedios Alemán, Víctor Asensi, María Eugenia Rivas Carmenado, Tomás Suárez‐Zarracina, Federico Pulido, Rafael Rubio, Otilia Bisbal, M. Asunción Hernando, David Rial, María Lagarde, Octavio Arce, Adriana Pinto, Laura Muñoz Bermejo, Mireia Santacreu, Roser Navarro, Candela Gonzalez, José Antonio Iribarren, María José Aramburu, Xabier Camino, Miguel Ángel von Wichmann, Miguel Ángel Goenaga, Ma Jesús Bustinduy, Harkaitz Azkune, Maialen Ibarguren, Xabier Kortajarena, Ignacio Álvarez-Rodriguez, Leire Gil, Lourdes Martínez, Félix Gutiérrez, Catalina Robledano, Mar Masiá, Sergio Padilla, Araceli Adsuar, Rafael J. Pascual, Marta Fernández, Antonio Galiana, José Alberto García, Xavier Barber, Vanessa Agullo, Javier García Abellán, Reyes Pascual, Guillermo Telenti, Lucía Guillén, Ángela Botella, Roberto Muga, Arantza Sanvisens, Daniel Fuster, Juan Berenguer, Isabel Gutiérrez, Juan Carlos López, Margarita Ramírez, Belén Padilla, Paloma Gijón, Teresa Aldámiz‐Echevarría, Francisco Tejerina, Cristina Díez, Leire Pérez, Chiara Fanciulli, Saray Corral, Francesc Vidal, Anna Martí, Joaquín Peraire, Consuelo Viladés, Montserrat Vargas, Montserrat Olona, Anna Rull, Verònica Alba, Elena Yeregui, Jenifer Masip, Graciano García‐Pardo, Fréderic Gómez-Bertomeu, Sonia Espineira, Marta Montero, Sandra Cuéllar, Marino Blanes, María Tasias, Eva Calabuig, Miguel Salavert, Juan Fernández, Inmaculada Segarra, Juan González‐García, Ana Sofia Delgado, Francisco Arnalich, José Ramón Arribas, José Ignacio Bernardino, Juan Castro, Luis Escosa, Pedro Herranz, Víctor Hontañón, Silvia García‐Bujalance, Milagros García, Alicia González, Luz Martín‐Carbonero, Mario Mayoral, María José Mellado, Rafael Esteban, Rocío Montejano, Marisa Montes, V. Moreno, Ignacio Valero, Berta Rodés, Guadalupe Rúa, Talía Sainz, Elena Sendagorta, Eulalia Valencia, Carmen Busca, Joanna Cano, Julen Cardiñanos, Rosa de Miguel, José Ramón Blanco, Laura Pérez‐Martínez, José A. Oteo, Valvanera Ibarra, Luís Metola, Mercedes Sanz, Piedad Arazo, Gloria Sampériz, David Dalmau, Marina Martínez, Ángeles Jaén, Montse Sanmartí, Mireia Cairó, Javier Martinez-Lacasa, Pablo Velli, Roser Font, Mariona Xercavins, Noemí Acedo Alonso, Tommaso Francesco Aiello, María Rivero, Beatriz Piérola, Maider Goikoetxea, María Pilar Rivero Gracia, Carlos Ibero, Estela Moreno-García, Jesús Repáraz, Gemma Navarro, Manel Cervantes Garcia, Sonia Calzado Isbert, Marta Navarro Vilasaró, Belen Lopez Garcia, Ignacio de los Santos, Alejandro de los Santos, Jesús Sanz, Lucio García‐Fraile, Enrique García Martín, Ildefonso Sánchez‐Cerrillo, Marta Calvet, Ana Barrios, Azucena Bautista, Carmen Sáez, Marianela Ciudad, Ángela Gutiérrez, Santiago Moreno, Santos del Campo, José L. Casado, Fernando Dronda, Ana Moreno, María Jesús Pérez-Granda, Sérgio Serrano, Ma Jesús Vivancos, Javier Martínez‐Sanz, Alejandro Vallejo, Matilde Sanchez, José A. Pérez‐Molina, José Manuel Hermida, Enrique Bernal, Antonia Alcaraz, Joaquín Bravo, Ángeles Muñoz, Cristina Tomás, Mónica Martínez, M. Carmen Villalba, Féderico García, Clara Martínez, Jose Luis Hernández‐Davó, Leopoldo Muñoz Medina, Marta Álvarez, Natalia Chueca, David Vinuesa, Adolfo de Salazar, Ana Fuentes, Emilio Guirao, Laura Viñuela, Andrés Ruiz-Sancho, Francisco Anguita, Jorge Del Romero, Montserrat Raposo, Carmen Rodríguez, Teresa Puerta, Juan Carlos Carrió, Mar Vera, Juan Ballesteros, Oskar Ayerdi, Begoña Baza, Eva Orviz, Antonio Antela, Elena Losada, Melchor Riera, María Luz Pintos Peñaranda, Ma Angels Ribas, Antoni A Campins, Mercedes Garcia-Gazalla, Francisco Fanjul, Javier Murillas, Francisco Homar, Helem Vílchez, Luisa Martı́n, Antoni Payeras, Jesús Santos, María López, Crisitina Gómez, Isabel Viciana, Rosario Palacios, Luís F. López‐Cortés, Núria Espinosa, Cristina Roca, Silvia Llaves, Juan Tiraboschi, Arkaitz Imaz, Ana Karina Silva, María Saumoy, Sofía Catalina Scévola, Adrián Curran, Vicenç Falcó, Jordi Navarro, Joaquín Burgos, Paula Suanzes, Jorge García, Vicente Descalzo, Patricia Álvarez, Bibiana Planas, Marta Sanchíz, Lucía Rodríguez, Julián Olalla, Matilde Sanchez, Javier Pérez, Alfonso del Arco, Javier de la Torre, José Luís Prada, Onofre Juan Martínez, Lorena Martinez‐Gamboa, Francisco Jesús Vera, Josefina García, Begoña Alcaraz, A. Guirao, Álvaro Mena, Ángeles Castro, Berta Pernas, Pilar Vázquez, Soledad López, Sofía Ibarra, Guillermo García, Josu Mirena, Oscar Luis Ferrero, Josefina López, Mari Mar Cámara, Mireia de la Peña, Miriam Lopez, Iñigo López, Itxaso Lombide, Víctor Polo, Joana Miguel, Carlos Galera, Marian Fernández, Helena Albendín, Antonia Navas Castillo, Asunción Iborra, Antonio Moreno, Maria Angustias Merlos, Asunción Vidal, Concha Amador, Francisco Pasquau, Concepcion Gil, José Tomás Algado, Inés Suárez‐García, Eduardo Malmierca, Patricia González‐Ruano, M. Pilar Ruiz, José Francisco Pascual, Elena Sáez, Luz Balsalobre, M. Villa López, Mohamed Omar, Carmen Herrero, M. Amparo Gómez, Miguel Alberto de Zárraga, Desiré Pérez, Vicente Estrada, Nieves Sanz, Noemí Cabello, Jorge Vergas García, Marı́a José Núñez, Íñigo Sagastagoitia, Miguel Górgolas, Alfonso Cabello, Beatriz Álvarez, Laura Lorente Prieto, Irene Carrillo, José Sanz, Alberto Arranz, Cristina Hernández, María Novella, Marı́a José Galindo, Ana Ferrer, Antonio Rivero Román, Inma Ruíz, Antonio Juárez, Pedro López López, Isabel Machuca, Mario Frías, Ángela Camacho, Ignacio Pérez, Diana Corona, Ignacio Pérez, Diana Corona, Miguel Cervero, Rafael Torres, Juan A. Pineda, Pilar Rincón, Juan Macı́as, Luís Miguel Real, Anaïs Corma, Marta Fernández, Alejandro González‐Serna, Eva Poveda, Alexandre Pérez‐González, Luís Morano, Celia Miralles, Antonio Ocampo, Guillermo Pousada, Lucía Patiño, Carlos Dueñas, Sara Gutiérrez, Elena Tapia, Cristina Novoa, Xjoylin Egües, Pablo Telleria - EBioMedicine 2023 cited by 40

BACKGROUND: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. METHODS: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. FINDINGS: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/μL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/μL, a CD8 count ≥1500 cells/μL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. INTERPRETATION: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/μL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. FUNDING: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.