Advances in host-directed therapy for tuberculosis and HIV coinfection: enhancing immune responses

Tuberculosis (TB) and HIV coinfection present a significant global health challenge worldwide. While most individuals infected with Mycobacterium tuberculosis (Mtb) have clinically asymptomatic latent TB infection (LTBI), those with immunosuppressive conditions, such as HIV, are at higher risk for reactivation and disseminated TB. HIV exacerbates TB progression by impairing immune responses, particularly through the depletion of Mtb-specific CD4⁺ T cells and chronic immune activation. Despite the success of combined antiretroviral therapy (cART) in managing HIV, it does not eliminate the risk of LTBI reactivation, highlighting the need for additional therapeutic strategies. Host-directed therapy (HDT) has emerged as a promising adjunct to current treatments. HDTs aim to restore immune function and counteract immune dysregulation caused by HIV, including T cell exhaustion and inflammation. This review explores key HDTs, including cytokine therapy, chimeric antigen receptor T cell (CAR-T cell) therapy and immune checkpoint inhibitors, which target Mtb-infected cells, enhance immune responses, and mitigate inflammation. By complementing cART and anti-TB therapy, HDTs could improve clinical outcomes by enhancing immune function, reducing inflammation, and preventing Mtb reactivation, offering hope for better management of TB/HIV coinfection.