{ "abstract": "Background: In sub-Saharan Africa where both tuberculosis (TB) and HIV are prevalent, empiric TB treatment in people living with HIV (PLHIV) persists due to limited sensitivity of sputum-based TB tests. We evaluated mortality among molecular test-negative presumptive TB adult PLHIV in a population with widespread antiretroviral therapy (ART) coverage, comparing those empirically treated and not treated for TB. Materials and methods: From November 2017 to December 2020, Xpert-negative adult PLHIV were recruited at Mulago Referral Hospital and Kisenyi Health Centre-IV in Kampala, Uganda. Clinical data including TB symptoms, chest X-ray, and empiric TB treatment decision were collected. Laboratory investigations included CD4 cell count, serum cryptococcal antigen (CrAg), urine TB-lipoarabinomannan (TB-LAM), microbiological blood cultures, and sputum mycobacterial growth indicator tube (MGIT) cultures. Participants were followed monthly for 12 months to ascertain vital status. Results: Overall, 300 participants were enrolled; 61.3% inpatients, 55.7% female, median age 37 (IQR 29–45) years, 82.3% on ART, median CD4 206 cells/mm³ (IQR 36–507). Of the 300, 68 (22.7%) received empiric TB treatment, of which 53 (77.9%) were inpatients. 12-month mortality was 31.0% (93/300); 72% within three months post-enrolment. TB cultures were positive in 5.0% (15/300), 12.3% had positive CrAg, and 3.7% had positive blood culture. Empirically treated participants had higher mortality (42.7%) than non-treated (27.6%) although the difference was not statistically significant after adjusting for factors indicative of severe illness (adjusted Mortality Rate Ratio- aMRR 1.05, p = 0.850). Inpatient (aMRR 3.80, p = 0.008) and poor functional status (aMRR 3.5 95%, p = 0.001) were independently associated with 12-month mortality. Conclusion: We found high 12-month mortality among Xpert-negative PLHIV, predominantly inpatients and within three months post-enrolment. Although empiric TB treatment was associated with higher mortality, this association was lost after adjustment for severe illness indicators. Cryptococcal antigenemia and bacteremia were not uncommon, underscoring need for comprehensive evaluations for non-TB conditions alongside empiric TB treatment.", "abstract_shown": true, "affiliations": [ "Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda", "Makerere University Biomedical Research Centre, Makerere University College of Health Sciences, Kampala, Uganda", "Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda", "Department of Pediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda", "Department of General Virology, Uganda Virus Research Institute, Entebbe, Uganda", "Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda", "Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, United States of America" ], "article_type": "Research Article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Lydia Nakiyingi" }, { "affs": [ 1 ], "name": "Bernard Kikaire" }, { "affs": [ 2 ], "name": "Sarah Nakayenga" }, { "affs": [ 3 ], "name": "Louis Kamulegeya" }, { "affs": [ 4 ], "name": "Elizabeth Nakabugo" }, { "affs": [ 5 ], "name": "Juliet Nkugwa Asio" }, { "affs": [ 6 ], "name": "Bernard Bagaya" }, { "name": "Willy Ssengooba" }, { "name": "Harriet Mayanja-Kizza" }, { "name": "Yukari C. Manabe" } ], "bibtex": "https://research.draconitic.com/paper/7kw6sezj9mf6r.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0347436", "fulltext_url": null, "id": "7kw6sezj9mf6r", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0347436", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2725|Tuberculosis Research and Epidemiology" ], [ "plos", "/Biology and life sciences/Immunology/Vaccination and immunization/Antiviral therapy/Antiretroviral therapy" ], [ "plos", "/Biology and life sciences/Organisms/Bacteria/Actinobacteria/Mycobacterium tuberculosis" ], [ "plos", "/Biology and life sciences/Population biology/Population metrics/Death rates" ], [ "plos", "/Medicine and health sciences/Diagnostic medicine" ], [ "plos", "/Medicine and health sciences/Diagnostic medicine/Tuberculosis diagnosis and management" ], [ "plos", "/Medicine and health sciences/Health care/Patients/Inpatients" ], [ "plos", "/Medicine and health sciences/Immunology/Vaccination and immunization/Antiviral therapy/Antiretroviral therapy" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Bacterial diseases/Tuberculosis" ], [ "plos", "/Medicine and health sciences/Medical conditions/Tropical diseases/Tuberculosis" ], [ "plos", "/Medicine and health sciences/Public and occupational health/Preventive medicine/Vaccination and immunization/Antiviral therapy/Antiretroviral therapy" ], [ "plos", "/People and places/Geographical locations/Africa/Uganda" ] ], "openalex": "W7150881846", "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0347436&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-08", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/7kw6sezj9mf6r.ris", "sources": [ { "first_seen": "2026-10-30T12:17:56Z", "native_id": "10.1371/journal.pone.0347436", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0347436" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "medicine", "origin": "plos:public and occupational health", "subfield": "epidemiology-public-health" }, { "field": "medicine", "origin": "plos:infectious diseases", "subfield": "infectious-disease" } ], "title": "Empiric tuberculosis treatment and 12-month mortality among sputum GeneXpert-negative adults living with HIV in Uganda in the era of widespread antiretroviral therapy: A prospective cohort study", "title_text": "Empiric tuberculosis treatment and 12-month mortality among sputum GeneXpert-negative adults living with HIV in Uganda in the era of widespread antiretroviral therapy: A prospective cohort study", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:56Z", "url": "https://research.draconitic.com/paper/7kw6sezj9mf6r", "venue": "PLOS One", "versions": [] }