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Clinical Trial
. 2025 May 14;25(1):695.
doi: 10.1186/s12879-025-10986-4.

Tuberculosis disease characteristics associated with mortality, severe morbidity and unsuccessful treatment in people living with HIV treated for tuberculosis - a secondary analysis of the ANRS 12300 Reflate TB2 trial

Robert Akpata  1 , Jean-Baptiste Ntakpe  2   3 , Eugène Messou  3   4   5 , Nathalie De Castro  2   6 , Corine Chazallon  2 , Isabel Timana  7 , Rodrigo Escada  8 , Sandra Wagner Cardoso  8 , Nilesh Bhatt  7 , Celso Khosa  7 , Didier Laureillard  9   10 , Giang Do Chau  11 , Frédéric Ello Nogbou  3   5 , Donald Diomande Glao  3   5 , Valdilea Veloso  7 , Jean-Michel Molina  6   12   13 , Beatriz Grinsztejn  7 , Marcel Zannou  14 , Serge Eholie  3   5 , Olivier Marcy  2 ; ANRS 12300 Reflate TB2 study Consortium
Collaborators, Affiliations
Clinical Trial

Tuberculosis disease characteristics associated with mortality, severe morbidity and unsuccessful treatment in people living with HIV treated for tuberculosis - a secondary analysis of the ANRS 12300 Reflate TB2 trial

Robert Akpata et al. BMC Infect Dis. .

Abstract

Background: Tuberculosis is a severe disease, not only due to its lethality but also to a significant morbidity occurring in people living with HIV (PLWH). If factors associated to mortality, severe morbidity and unsuccessful treatment related to the host are well identified in PLWH, there is scarce knowledge on factors related to the disease itself such as bacillary load, extent of lung involvement and disease dissemination to other organs. We sought to assess whether tuberculosis-related factors were associated with key patient outcomes in PLWH using data from an international clinical trial.

Methods: We conducted a secondary analysis of the ANRS 12300 Reflate TB2, an international phase III open-label randomized trial that assessed different antiretroviral regimens in PLWH treated for tuberculosis. We evaluated whether bacillary load (smear positivity grade), extent of lung involvement (cavitation on chest x-ray) and disease dissemination (urine LAM positivity) were associated with mortality using Cox proportional hazard models, and to severe morbidity and unsuccessful tuberculosis treatment using logistic regressions.

Results: Of 457 participants included in this study, 90 (20.4%) had grade 2 + or 3 + smear positivity, 39 (10.8%) had cavitation on chest X-ray, and 147 (32.2%) had a positive urinary LAM. Overall, 19 (4.2%) participants died, 113 (24.7%) presented severe morbidity, and 33 (7.2%) had unsuccessful tuberculosis treatment. Factors that remained independently associated with mortality were cavitation on chest x-ray (aHR = 7.92, 95% CI, 1.74-35.94, p = .0073) and LAM positivity (aHR = 5.53, 95% CI, 1.09-28.06, p = .0389). The only factor that remained significantly associated with severe morbidity was LAM positivity (aOR = 2.04, 95% CI, 1.06-3.92, p = .0323). No factor remained significantly associated with unsuccessful tuberculosis treatment.

Conclusions: In PLWH with tuberculosis enrolled in a trial, tuberculosis disease characteristics related to disease severity were cavitation on chest x-ray and urine LAM positivity. Early identification of these factors could help improve the management of PLWH with tuberculosis and improve their survival.

Keywords: Bacillary load; Disease dissemination; Extent of lung involvement; HIV; Mortality; Severe morbidity; Tuberculosis; Unsuccessful treatment.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by Comité National d’Ethique et de la Recherche (Côte d’Ivoire), CEP IPEC (Brazil), Comité de Protection des Personnes Ile-de-France II (France), Comitê Nacional de Bioética para Saúde (Mozambique) and IRB PNTH (Vietnam). The ANRS 12300 Reflate TB2 trial protocol was registered with ClinicalTrials.gov (NCT02273765, 22 October 2014) and was conducted in accordance with the Declaration of Helsinki. All participants provided signed informed consent before enrollment in the main trial. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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