Prioritizing Tuberculosis Preventive Therapy for IGRA-negative People Living with HIV Initiating Antiretroviral Therapy

Background Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLWH). While tuberculosis preventive treatment (TPT) is universally recommended for PLWH with latent TB infection (LTBI), its necessity for interferon-gamma release assay (IGRA)-negative individuals initiating antiretroviral therapy (ART) is controversial. Therefore, this study aimed to investigate whether TPT is necessary in this specific population. Methods We conducted a retrospective cohort study of ART-naïve PLWH with a negative IGRA without prior anti-tuberculosis drug use or active TB at Shanghai Public Health Clinical Center from 2020 to 2024. Demographic characteristics, laboratory results, and TB occurrence during follow-up were recorded. Kaplan-Meier analysis, Cox proportional hazards models, and restricted cubic splines were used to identify risk factors and model the dose-response relationship between CD4+ T-cell count and TB risk. Results Among 686 participants (89.4% male, median age 41), the median CD4+ T-cell count was 35.52 cells/µL. During a 26-month median follow-up, 22 patients developed TB (incidence: 13.41/1000 person-years). All TB cases occurred in the 583 patients with CD4+ T-cell count < 200 cells/µL (incidence: 15.61/1000 person-years), while no events occurred in those with CD4+ T-cell count ≥ 200 cells/µL. Lower CD4+ T-cell count and residence in high-risk areas (adjusted Hazard Ratio [aHR] = 3.65, 95% CI: 1.35-9.89) were independent risk factors for active TB. A continuous log-linear inverse relationship between CD4+ T-cell count and TB risk was identified, with progressively higher risk at lower CD4 levels. Conclusion IGRA-negative PLWH with CD4+ T-cell count < 200 cells/µL and high-risk area residence may be considered as priority candidates for TPT. This risk-stratification framework warrants prospective validation.