Advances in host-directed therapies for tuberculosis

Tuberculosis (TB) treatment is lengthy and complex, requiring patients to adhere to multidrug regimens, which may be difficult to tolerate. Importantly, traditional antimicrobial therapy does not prevent infection-associated lung damage. Adjunctive host-directed therapies (HDTs) could address the issues associated with standard antitubercular therapy. We highlight recent advances in pulmonary TB HDT clinical trials and discuss the molecular pathways targeted, focusing on approaches that future research can build on to develop new TB regimens that may include HDTs.

We review results from recent clinical studies registered on https://clinicaltrials.gov/ and we present a summary of the state of the art in TB HDT development. We provide a list of leading candidates and discuss their phase of development in the clinical pipeline.

Complementary approaches have been used to evaluate acceleration of sputum culture conversion, amelioration of lung inflammation, and prevention of lung damage in the clinical studies described. Despite a lengthy list of HDT candidates evaluated in human studies, none to date has shown benefit in accelerating sputum culture conversion, although successes in reducing biomarkers of lung damage have been reported. Continued research that includes the use of innovative biomarkers may reveal important roles for HDTs as adjunctive therapies for TB treatment.