Prevalence and mortality due to <i>Mycobacterium tuberculosis</i> bloodstream infection in adults with HIV: a multi-country prospective cohort study

Background HIV-associated tuberculosis is a leading cause of mortality. Mycobacterium tuberculosis bloodstream infection (MTB-BSI) is complicated by diagnostic difficulty and severe illness. We assessed whether MTB-BSI continues to be common in the era of widespread ART and whether it continues to result in increased risk of early mortality. Methods We enrolled inpatients from medical wards (irrespective of tuberculosis symptoms) and outpatients (with tuberculosis symptoms) who were living with HIV and ≥18 years from seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Vietnam and Zambia). Participants also had fewer than three doses of anti-tuberculosis treatment (past sixty days) and no isoniazid preventive therapy (past six months). We estimated the prevalence of MTB-BSI. In Bayesian survival models, we estimated the hazards of mortality in inpatients with MTB-BSI compared to those without. Results Between 2019 and 2021, 1703 participants were included: 44% were hospitalised; median CD4 361 cells/μL; 77% reported using ART. Crude prevalence of MTB-BSI varied by country but was 4.4% (n=32/723) among all inpatients, 22.5% (n=32/142) amongst inpatients with microbiologically-confirmed TB, and 0.2% (n=2/913) among all outpatients. Among all inpatients, those with MTB-BSI had 2.65 (95%CrI: 1.06-5.01) increased hazard of death by 30 days and 1.79 increased hazard by 70 days (95%CrI: 0.81-3.11). Lower CD4 and older age were strongly associated with mortality. Conclusions MTB-BSI is far more common in inpatients than outpatients with HIV. Across multiple high tuberculosis prevalence settings, MTB-BSI was strongly associated with heightened risk of early mortality in PWH. Novel, optimised diagnostic and treatment strategies are still needed for HIV-associated MTB-BSI.