A Pan-TB Regimen Targeting Host and Microbe (panTB-HM)

Inclusion Criteria: Aged 18 to 65 years Willing and able to provide signed written consent prior to undertaking any trial-related procedures, or, in the case of illiteracy, witnessed oral consent Body weight (in light clothing without shoes) between 30 and 90 kg. Radiographic evidence of pulmonary tuberculosis Positive Xpert TB/RIF (original or Ultra) for MTB RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation If sexually active, willing to use an effective contraceptive method for the duration of tuberculosis treatment HIV-1 seronegative, or if HIV-1 seropositive, CD4 T cell count ≥100/µl and either receiving ART or willing to start ART during study participation SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 or with D-dimer <0.8 ug/ml Willing to adhere to a diet excluding tyramine-rich foods (certain mold-ripened cheeses and cured meats), and to avoid eating grapefruits and pomelos Exclusion Criteria: Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments Current or imminent (within 24 hr) treatment for malaria. Pregnant or nursing Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period. TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator. History of allergy or hypersensitivity to any of the trial therapies or related substances. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial. Prior TB treatment in the preceding 6 months Angina pectoris requiring treatment with nitroglycerin or other nitrates Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator History of unstable Diabetes Mellitus requiring hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening. Use of systemic corticosteroids within the past 28 days. Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors Patients requiring treatment with antidepressants, including MAO inhibitors and SSRIs. Subjects with any of the following abnormal laboratory values: HBsAg positive creatinine >2 mg/dL hemoglobin <8 g/dL platelets <100x109 cells/L serum potassium <3.5 mM/L alanine aminotransferase (ALT) ≥2.0 x ULN alkaline phosphatase (AP) >5.0 x ULN total bilirubin >1.5 mg/dL random blood glucose >200 mg/dL