Host-directed therapy for tuberculosis: Repurposed drugs toward global tuberculosis elimination

Area of Science:

• Infectious Diseases
• Immunology
• Pharmacology

Background:

• Tuberculosis (TB) remains a leading global infectious cause of death, with conventional treatments facing challenges like prolonged duration and drug toxicity.
• Host-directed therapies (HDTs) are emerging as a crucial adjunctive strategy to improve TB treatment outcomes by enhancing bacterial clearance and reducing host-induced pathology.

Purpose of the Study:

• To review mechanistic and clinical evidence for repurposed, affordable agents as host-directed therapies (HDTs) for tuberculosis (TB).
• To categorize HDT candidates by targeted host pathways and assess their relevance in various TB forms and comorbidities.

Main Methods:

• Systematic review of mechanistic and clinical evidence for repurposed agents as HDTs.
• Categorization of HDT candidates based on targeted host pathways (e.g., autophagy, inflammation, lipid metabolism).
• Evaluation of HDT relevance in pulmonary and extrapulmonary TB, and associated comorbidities like HIV and diabetes.

Main Results:

• Multiple host pathways are targeted by repurposed agents, including autophagy (metformin, vitamin D), inflammation (NSAIDs), and lipid metabolism (statins).
• HDTs show potential benefits across different TB forms and in patients with comorbidities such as HIV and diabetes mellitus.
• Evidence from randomized controlled trials supports the potential of certain HDTs, but large-scale Phase III trials are needed.

Conclusions:

• Integrating host-directed therapies (HDTs) alongside conventional antimicrobial treatments is essential for accelerating global TB elimination efforts.
• Further large-scale, stratified Phase III trials are required to transition promising HDT candidates into standard clinical practice for tuberculosis management.