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Background <p>Tuberculosis (TB) incidence among people with HIV (PWH) has fallen in many high-income settings, yet residual risk persists, and tools to identify those still vulnerable are limited. This study aimed to evaluate TB incidence trends, identify risk factors, and develop a predictive score in PWH in Spain.</p> Methods <p>We conducted a retrospective nationwide cohort study using the Spanish AIDS Research Network (CoRIS). Adults initiating antiretroviral therapy (ART) between 2004 and 2023 were followed from ART start until incident TB, death, or censoring. Incidence rates were expressed per 1000 person-years; temporal trends were evaluated across four calendar periods. Independent risk factors were identified with multivariable Cox models, and a predictive score was internally validated with bootstrapping and ROC analysis.</p> Results <p>Among 16,476 PWH contributing 50,414 person-years, 61 developed TB, yielding an overall incidence of 1.21 cases/1000 person-years (95% <i>CI</i> 0.94–1.56). TB incidence rate declined by 97% between 2004–2008 and 2019–2023 (from 9.1 to 0.2 cases per 1000 person-years<i>; IRR</i> = 0.026, 95% <i>CI</i> 0.004–0.19). Injection-drug use (<i>HR</i> = 2.6, 95% <i>CI</i> 1.21–5.66), low educational attainment (<i>HR</i> = 2.8, 95% <i>CI</i> 1.05–7.51), baseline HIV-RNA viral load &gt; 1 million copies/ml (<i>HR</i> = 1.7, 95% <i>CI</i> 1.00–2.82) and positive latent-TB infection (LTBI) screening (<i>HR</i> = 3.5, 95% <i>CI</i> 1.79–7.01) independently predicted incident TB. A four-variable model showed good discrimination (<i>AUC</i> = 0.71, 95% <i>CI</i> 0.65–0.77).</p> Conclusion <p>Universal ART and comprehensive LTBI management have driven a large decrease in TB incidence in Spanish PWH, but a small subset—characterised by social vulnerability, high viraemia and positive LTBI tests—remains at elevated risk. The validated risk score offers a pragmatic tool to target preventive therapy and surveillance where most needed in low-incidence, high-care settings.</p>

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Towards tuberculosis elimination in people with HIV on antiretroviral therapy: evidence from a two-decade nationwide cohort in Spain

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  • 发表日期：

    2026年3月6日

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  • Roser Navarro-Soler,
  • Alfonso Muriel,
  • Chiara Fanciulli,
  • José I. Bernardino,
  • Carmen Sáez,
  • Javier Zamora,
  • Borja M. Fernandez-Felix,
  • Alejandro G. García-Ruíz de Morales,
  • Eva Poveda,
  • Álvaro Mena de Cea,
  • Javier Martínez-Sanz,
  • Santiago Moreno,
  • Sergio Serrano-Villar,
  • Inma Jarrín,
  • David Dalmau,
  • M Luisa Navarro,
  • M Isabel González,
  • Federico Garcia,
  • Jose Antonio Iribarren,
  • Félix Gutiérrez,
  • Rafael Rubio,
  • Francesc Vidal,
  • Juan Berenguer,
  • Juan González,
  • M Ángeles Muñoz-Fernández,
  • Inmaculada Jarrín,
  • Cristina Moreno,
  • Marta Rava,
  • Rebeca Izquierdo,
  • Cristina Marco,
  • Teresa Gómez-García,
  • Ma Ángeles Muñoz-Fernández,
  • Roxana Juárez,
  • Joaquín Portilla,
  • Irene Portilla,
  • Esperanza Merino,
  • Gema García,
  • Iván Agea,
  • José Sánchez-Payá,
  • Juan Carlos Rodríguez,
  • Livia Giner,
  • Sergio Reus,
  • Vicente Boix,
  • Diego Torrus,
  • Verónica Pérez,
  • Julia Portilla,
  • Héctor Pinargote,
  • María Remedios Alemán,
  • Ana López Lirola,
  • Dácil García,
  • Felicitas Díaz-Flores,
  • M Mar Alonso,
  • Ricardo Pelazas,
  • María Inmaculada Hernández,
  • Lucia Romero,
  • Abraham Bethencourt,
  • Daniel Rodríguez,
  • Víctor Asensi,
  • Rebeca Cabo Magadan,
  • Lorena Fernández,
  • Javier Díaz-Arias,
  • Federico Pulido,
  • Rafael Rubio,
  • Otilia Bisbal,
  • M Asunción Hernando,
  • David Rial,
  • María de Lagarde,
  • Adriana Pinto,
  • Laura Bermejo,
  • Mireia Santacreu,
  • Roser Navarro Soler,
  • Juan Martín Torres,
  • José Antonio Iribarren,
  • M José Aramburu,
  • Xabier Camino,
  • Miguel Ángel Goenaga,
  • M Jesús Bustinduy,
  • Harkaitz Azkune,
  • Maialen Ibarguren,
  • Xabier Kortajarena,
  • Ignacio Álvarez-Rodriguez,
  • Leire Gil,
  • Francisco Carmona-Torre,
  • Ana Bayona Carlos,
  • Maialen Lekuona Sanz,
  • Claudia Nevado Pavón,
  • Félix Gutiérrez,
  • Catalina Robledano,
  • Mar Masiá,
  • Sergio Padilla,
  • Rafael Pascual,
  • Marta Fernández,
  • Antonio Galiana,
  • José Alberto García,
  • Xavier Barber,
  • Javier García Abellán,
  • Guillermo Telenti,
  • Ángela Botella,
  • Paula Mascarell,
  • Mar Carvajal,
  • Lidia García-Sánchez,
  • Nuria Ena,
  • Leandro López,
  • Jennifer Vallejo,
  • Nieves Gonzalo-Jiménez,
  • Montserrat Ruiz,
  • Christian Ledesma,
  • Santiago López,
  • María Espinosa,
  • Ana Quiles,
  • María Andreo,
  • María del Mar Alcalde,
  • José García,
  • Rosario Hernández,
  • José Carlos Escribano,
  • Marouane Menchi,
  • María del Mar García Navarro,
  • Juan Carlos López Bernaldo de Quirós,
  • Isabel Gutiérrez,
  • Juan Berenguer,
  • Margarita Ramírez,
  • Paloma Gijón,
  • Teresa Aldamiz-Echevarría,
  • Francisco Tejerina,
  • Cristina Diez,
  • Leire Pérez,
  • Saray Corral,
  • Joaquín Peraire,
  • Anna Rull,
  • Anna Martí,
  • Consuelo Viladés,
  • Beatriz Villar,
  • Lluïsa Guillem,
  • Silvia Chafino,
  • Marina Flores,
  • Marta Montero-Alonso,
  • María Tasias,
  • Eva Calabuig,
  • Miguel Salavert,
  • Juan Fernández,
  • Rosa Blanes,
  • Jennifer Sánchez,
  • Juan González-García,
  • Ana Delgado-Hierro,
  • José Ramón Arribas,
  • Víctor Arribas,
  • José Ignacio Bernardino,
  • Carmen Busca,
  • Joanna Cano-Smith,
  • Julen Cadiñanos,
  • Juan Miguel Castro,
  • Luis Escosa,
  • Iker Falces,
  • Pedro Herranz,
  • Víctor Hontañón,
  • Alicia González-Baeza,
  • M Luz Martín-Carbonero,
  • Mario Mayoral,
  • Rafael Micán,
  • Rosa de Miguel,
  • Rocío Montejano,
  • Ma Luisa Montes,
  • Luis Ramos-Ruperto,
  • Berta Rodés,
  • Talía Sainz,
  • Elena Sendagorta,
  • Eulalia Valencia,
  • M del Mar Arcos,
  • Alejandro de Gea Grela,
  • Carlos Oñoro López,
  • David Dalmau,
  • Marina Martinez,
  • Angels Jaén,
  • Mireia Cairó,
  • Javier Martinez-Lacasa,
  • Roser Font,
  • Laura Gisbert,
  • Ignacio de los Santos,
  • Alejandro de los Santos,
  • Lucio García-Fraile,
  • Enrique Martín,
  • Ildefonso Sánchez-Cerrillo,
  • Marta Calvet,
  • Ana Barrios,
  • Azucena Bautista,
  • Marianela Ciudad,
  • Ángela Gutiérrez,
  • María Aguilera García,
  • Violeta Sampériz Rubio,
  • Santos del Campo,
  • José Luis Casado,
  • Fernando Dronda,
  • Ana Moreno,
  • M Jesús Pérez,
  • Ma Jesús Vivancos,
  • Alejandro Vallejo,
  • Matilde Sánchez,
  • José Antonio Pérez-Molina,
  • José Manuel Hermida,
  • Erick de La Torre Tarazona,
  • Elena Moreno,
  • Laura Martín Pedraza,
  • Claudio Díaz García,
  • Jorge Díaz,
  • Alejandro García,
  • Raquel Ron,
  • Enrique Bernal,
  • Antonia Alcaraz,
  • Joaquín Bravo,
  • Ángeles Muñoz,
  • Cristina Tomás,
  • Eva Oliver,
  • Eva García,
  • Román González,
  • Elena Guijarro,
  • Rodrigo Martínez,
  • María Dolores Hernández,
  • Federico García,
  • Clara Martínez,
  • Leopoldo Muñoz Medina,
  • Marta Álvarez,
  • Natalia Chueca,
  • David Vinuesa,
  • Adolfo de Salazar,
  • Ana Fuentes,
  • Emilio Guirao,
  • Andrés Ruiz-Sancho,
  • Francisco Anguita,
  • Naya Faro,
  • Lucia Chaves,
  • Marta Illescas,
  • Paloma Muñoz,
  • Lucía Pérez,
  • Jorge Del Romero,
  • Montserrat Raposo,
  • Teresa Puerta,
  • Mar Vera,
  • Juan Ballesteros,
  • Begoña Baza,
  • Eva Orviz,
  • Manuel Sanchez Robledo,
  • Laura Dans Villán,
  • Ruben Linares Navarro,
  • Ines Armenteros Yeguas,
  • Melchor Riera,
  • María Peñaranda,
  • M Angels Ribas,
  • Antoni A Campins,
  • Mercedes Garcia-Gasalla,
  • Francisco J Fanjul,
  • Javier Murillas,
  • Luisa Martin-Pena,
  • Francisca Artigues,
  • Sophia Pinecki,
  • Jesús Santos,
  • María López-Jódar,
  • Cristina Gómez-Ayerbe,
  • Isabel Viciana,
  • Rosario Palacios,
  • Luis Fernando López-Cortés,
  • Nuria Espinosa,
  • Cristina Roca,
  • Silvia Llaves,
  • Marta Herreros,
  • César Sotomayor,
  • Juan Manuel Tiraboschi,
  • Arkaitz Imaz,
  • María Saumoy,
  • Analuz Fernandez,
  • Jaime Vega Costa,
  • Daniel Medina Gamito,
  • Julián Olalla,
  • Javier Pérez,
  • Alfonso del Arco,
  • Javier de la Torre,
  • José Luis Prada,
  • Onofre Juan Martínez,
  • Lorena Martinez,
  • Francisco Jesús Vera,
  • Josefina García,
  • Begoña Alcaraz,
  • Sergio Guillén Martínez,
  • Patricia Carles García,
  • Álvaro Mena,
  • Berta Pernas,
  • Pilar Vázquez,
  • Soledad López,
  • Brais Castelo,
  • Carlos Galera,
  • Marian Fernández,
  • Helena Albendin,
  • Antonia Castillo,
  • Asunción Iborra,
  • Antonio Moreno,
  • M Angustias Merlos,
  • Almudena Ortuño,
  • Inés Suarez-García,
  • Eduardo Malmierca,
  • Patricia González-Ruano,
  • M Pilar Ruiz,
  • Luz Balsalobre,
  • Ángela Somodevilla,
  • Rebeca Fuerte Martínez,
  • Vicente Estrada,
  • Noemí Cabello,
  • María José Núñez,
  • Juncal Pérez-Somarriba,
  • Reynaldo Homen,
  • Ana Muñoz,
  • Julia Barrado,
  • Maravillas Carralon,
  • Nieves Sanz,
  • Susana Olmedo,
  • José Sanz,
  • Cristina Hernández,
  • María Novella,
  • María José Galindo,
  • Sandra Pérez Gómez,
  • Ana Ferrer,
  • Antonio Rivero Román,
  • Antonio Rivero Juárez,
  • Pedro López,
  • Mario Frias,
  • Ángela Camacho,
  • Ignacio Pérez,
  • Diana Corona,
  • Javier Manuel Caballero,
  • Laura Ruiz Torres,
  • Ángela Carrasco,
  • Marina Gallo Marín,
  • María Casares,
  • Lucía Rios Muñoz,
  • Rafael Rodríguez-Rosado Martinez-Echevarría,
  • Rafael Torres,
  • Juan Macías Sánchez,
  • Pilar Rincón,
  • Luis Miguel Real,
  • Anaïs Corma,
  • Jésica Martín,
  • Alexandre Pérez,
  • Luis Morano,
  • Celia Miralles,
  • Antonio Ocampo,
  • Jacobo Alonso,
  • Inés Martínez,
  • Aida López

摘要

Background

Tuberculosis (TB) incidence among people with HIV (PWH) has fallen in many high-income settings, yet residual risk persists, and tools to identify those still vulnerable are limited. This study aimed to evaluate TB incidence trends, identify risk factors, and develop a predictive score in PWH in Spain.

Methods

We conducted a retrospective nationwide cohort study using the Spanish AIDS Research Network (CoRIS). Adults initiating antiretroviral therapy (ART) between 2004 and 2023 were followed from ART start until incident TB, death, or censoring. Incidence rates were expressed per 1000 person-years; temporal trends were evaluated across four calendar periods. Independent risk factors were identified with multivariable Cox models, and a predictive score was internally validated with bootstrapping and ROC analysis.

Results

Among 16,476 PWH contributing 50,414 person-years, 61 developed TB, yielding an overall incidence of 1.21 cases/1000 person-years (95% CI 0.94–1.56). TB incidence rate declined by 97% between 2004–2008 and 2019–2023 (from 9.1 to 0.2 cases per 1000 person-years; IRR = 0.026, 95% CI 0.004–0.19). Injection-drug use (HR = 2.6, 95% CI 1.21–5.66), low educational attainment (HR = 2.8, 95% CI 1.05–7.51), baseline HIV-RNA viral load > 1 million copies/ml (HR = 1.7, 95% CI 1.00–2.82) and positive latent-TB infection (LTBI) screening (HR = 3.5, 95% CI 1.79–7.01) independently predicted incident TB. A four-variable model showed good discrimination (AUC = 0.71, 95% CI 0.65–0.77).

Conclusion

Universal ART and comprehensive LTBI management have driven a large decrease in TB incidence in Spanish PWH, but a small subset—characterised by social vulnerability, high viraemia and positive LTBI tests—remains at elevated risk. The validated risk score offers a pragmatic tool to target preventive therapy and surveillance where most needed in low-incidence, high-care settings.