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

TL;DR

This study shows that TB rates in HIV patients on ART in Spain have dropped significantly, but some high-risk groups remain, and a new risk score helps identify them.

Contribution

A validated predictive risk score for TB in HIV patients on ART, based on a two-decade nationwide cohort in Spain.

Findings

TB incidence in HIV patients on ART in Spain decreased by 97% from 2004–2008 to 2019–2023.

Key risk factors for TB included injection-drug use, low education, high HIV viral load, and positive latent TB infection.

A four-variable predictive model showed good discrimination (AUC = 0.71) for identifying high-risk individuals.

Abstract

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.

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.

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).

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.

The online version contains supplementary material available at 10.1186/s40249-026-01426-9.

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