HE INFLUENCE OF HIV INFECTION ON THE PROCESSES OF LUNG TISSUE REMODELING IN TUBERCULOSIS PATIENTS DURING ANTI-TB TREATMENT

Abstract

The adaptive immune response to tuberculosis develops approximately six weeks after infection. In HIV, this process is disrupted due to delayed activation of CD4 lymphocytes. Immune cells in combination with mycobacteria stimulate the synthesis of matrix metalloproteinase-9 (MMP-9), which breaks down collagen. Its breakdown product (hydroxyproline) is a biomarker of lung tissue destruction. The ratio of MMP-9 to tissue inhibitor of metalloproteinases-1 (TIMP-1) (MMP-9/TIMP-1) reflects the balance between degradation and repair of lung tissue. In addition, aldosterone plays an important role, as it can activate monocytes, enhance inflammation, disrupt fibrinolysis, and stimulate collagen synthesis by fibroblasts. Its elevated level is associated with the development of pulmonary fibrosis. In patients with MDR-TB without HIV infection, the processes of pulmonary tissue remodeling were more typical: the balance between MMP-9, TIMP-1, and hydroxyproline was maintained, which contributed to the development of fibrosis and limitation of inflammation. In patients with TB/HIV coinfection, there was a marked imbalance in fibrosis factors: increased levels of MMP-9 and hydroxyproline with insufficient activation of TIMP-1, which led to a more generalized process and worse clinical outcomes. Aldosterone levels decreased during treatment in both groups, but this decrease was less pronounced in TB/HIV patients, confirming abnormalities in the fibrosis system in this group of patients.