Table 1.

Host-Directed Therapies against TB: Recent Clinical and Additional Studies.

Candidate	Description	Results	Remarks	References
1. Clinical Studies
Everolimus, Auranofin, Vitamin D, CC-11050	Combination therapy of HDT with DOTS drug regimen, followed with a modified DOTs protocol for 4 months with the intent to improve efficacy and outcomes of TB	Active, not enrolling.	Randomized, phase 2 clinical trial in South Africa	ClinicalTrials.gov Identifier: NCT02968927 [48,49]
Azithromycin	Immunomodulatory, adjunctive HDT therapy on top of the current DOTs regimen to reduce excessive inflammation, tissue degradation, and improve clinical outcomes of TB	Active, enrolling	Prospective, randomized, phase 2 pilot study in the Netherlands	ClinicalTrials.gov Identifier: NCT03160638
N-acetylcysteine	N-acetylcysteine in conjunction with rifampicin, isoniazid, pyrazinamide, ethambutol to provide anti-TB and antioxidative effects for patients with active HIV/TB infections	Active, enrolling	Randomized, phase 2 clinical trial in Brazil	ClinicalTrials.gov Identifier: NCT03281226
Vitamin D	Adjunctive vitamin D therapy in combination to standard antibiotic treatment for pulmonary tuberculosis to potentially enhance patient response	Vitamin D supplementation did not significantly reduce sputum conversion time among study population	Double-blind, randomized phase 3 clinical trial in the United Kingdom	ClinicalTrials.gov Identifier: NCT00419068 [50]
	Vitamin D supplementation to standard DOTs therapy with the hopes of quicker patient recovery times (demonstrated by sputum culture conversion)	Vitamin D supplementation did not significantly reduce sputum conversion time	Double-blind, randomized, placebo-controlled phase 3 clinical trial in South India	ClinicalTrials.gov Identifier: NCT00366470 [51]
	Effects of adjunctive vitamin D on host immunity with respect to TB and response to appropriate treatment	High-dose vitamin D3 corrected deficiency among patient, but did not improve TB clearance over the course of the trial	Double-blind, randomized, controlled phase 2 clinical trial in the United States	ClinicalTrials.gov Identifier: NCT00918086 [52]
	Determining if replacement of vitamin D in deficient patients with active TB affects clinical outcome	Vitamin D in high doses resulted in improvement in all TB patients, including those with vitamin D deficiencies.	Randomized, placebo-controlled clinical trial in Pakistan	ClinicalTrials.gov Identifier: NCT01130311 [53,54]
	Vitamin D and L-arginine supplementation in diagnosed TB patients in order to improve clinical outcomes and responses to pulmonary TB	With the doses administered, neither vitamin D nor L-arginine supplementation affected TB outcomes	Randomized, double-blind, placebo-controlled phase 3 clinical trial in Indonesia	ClinicalTrials.gov Identifier: NCT00677339 [55]
	Vitamin D3 and phenylbutyrate supplementation to standard short course DOTS therapy in order to improve recovery times and improve clinical outcomes in newly diagnosed TB patients	Beneficial effects towards patient recovery has been observed with phenylbutyrate, vitamin D3, or combination of phenylbutyrate and vitamin D3 supplementation with standard short-course therapy	Randomized, double-blind, placebo-controlled, 4-arm Phase 2 clinical trial in Bangladesh	ClinicalTrials.gov Identifier: NCT01580007 [28]
2. Additional Studies
Metformin	Multiple studies investigating the supplementation of metformin to existing standard anti-tuberculosis therapies, specifically in application to diabetic-TB patients	Metformin as an adjunctive therapy for diabetic TB patients needs to be understood further, even at the clinical level, due to inconsistent outcome reporting across studies	Retrospective cohort or case control studies. While there are reports of positive effects of metformin on active TB infections, there has been reports of no significant benefits in utilizing metformin as an adjunctive therapy.	[38,39,56,57,58,59]
Statins	Studies sought to understand the usage of cholesterol-lowering lipids (i.e., statins) and outcomes in regard to TB infections	Statins show beneficial effects as adjunctive therapy in TB infected M. marinum TB, and have been observed to shorten the culture negativity, reduce tissue pathology, and enhance bacterial killing along standard TB therapy. However, statins did not prevent TB progression in individuals who were newly diagnosed with type 2 diabetes mellitus.	Further studies will need to be conducted in order to understand the effects of statins and other potential cholesterol-lowering drugs on recovery times and outcome improvement in TB infections.	[42]