Elevated plasma matrix metalloproteinases associate with <i>Mycobacterium tuberculosis</i> blood stream infection and mortality in HIV-associated tuberculosis

Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality and <i>Mycobacterium tuberculosis</i> (<i>Mtb)</i> blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in <i>Mtb</i>-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated with <i>Mtb</i>-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.