Objective To explore the clinical characteristics of AIDS patients complicated with tuberculosis who had negative interferon-γ release assay results for Mycobacterium tuberculosis. Methods Clinical data of 127 hospitalized AIDS patients, who were complicated with tuberculosis and had negative interferon-γ release assay results for Mycobacterium tuberculosis, who were admitted to The Fourth People's Hospital of Nanning from January 2020 to June 2023, were retrospectively collected. Their sociodemographic characteristics, tuberculosis diagnostic categories and lesion locations, other co-existing opportunistic infections, clinical manifestations, laboratory findings, chest imaging features, and outcomes after anti-tuberculosis and antiretroviral therapy (ART) were analyzed. Results Among the 127 patients, 103 were male and 24 were female, with a median age of 49 years. Fifty-six cases (44.09%) were confirmed and 71 cases (55.91%) were clinically diagnosed. 74.80% (95/127) of patients had baseline CD4+ T-lymphocyte counts < 100 cells/μL, and the rate of co-existing other opportunistic infections reached 65.35% (83/127). The predominant clinical manifestations included cough with expectoration (75.59%), fever (59.06%), and weight loss (57.48%), whereas classic tuberculous toxic symptoms (night sweats, hemoptysis) were uncommon. Extrapulmonary tuberculosis accounted for 37.80% (48/127), frequently involving lymph nodes, abdominal cavity, and central nervous system. Chest CT showed that 76.38% (97/127) of patients mainly presented with scattered exudative lesions, while cavitation was seen in only 12.60% of patients. The overall etiological positive detection rate was 44.09% (56/127), including 29 positive acid-fast bacilli smears, 37 positive Mycobacterium tuberculosis complex cultures, and 38 positive nucleic acid tests for Mycobacterium tuberculosis complex (23 positive by Xpert MTB/RIF assay). After standardized treatment, 67.72% (86/127) achieved favorable tuberculosis outcomes; patients' CD4+ T-lymphocyte counts increased compared with baseline after 1-year ART (P<0.05). The incidence of immune reconstitution inflammatory syndrome was 11.81% (15/127), all occurring within 1 month after ART initiation; the incidence of adverse drug reactions was 13.39% (17/127), dominated by liver function injury. Up to 6 months after completion of anti-tuberculosis therapy, 18 patients died (14.17%), among whom 15 had baseline CD4+ T-lymphocyte counts <100 cells/μL and 11 died within the first 3 months of treatment. Conclusion Most AIDS patients with concurrent tuberculosis who test negative on the interferon-γ release assay for Mycobacterium tuberculosis present with severe immunosuppression, presenting with atypical clinical manifestations, high incidence of extrapulmonary tuberculosis and mixed opportunistic infections, and predominantly diffuse exudative lesions on chest imaging; additionally, pathogen detection is difficult, making the diagnosis highly challenging. Nevertheless, most patients can achieve satisfactory outcomes once standardized anti-tuberculosis therapy combined with ART is initiated. In clinical practice, tuberculosis should not be readily ruled out for this population even with negative Mycobacterium tuberculosis interferon-γ release assay results. Combined molecular assays and multi-site specimen collection should be actively performed to improve the diagnostic rate.

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