Adjunctive Acetylsalicylic Acid and Ibuprofen for Tuberculosis

Inclusion Criteria:

1. Adults, 18- 60 years of age
2. Written informed consent in a language they understand. This includes informed consentto be in the trial and informed consent to collect specimens.
3. Laboratory confirmed pulmonary TB (with or without extrapulmonary involvement) definedas a hard copy of a sputum laboratory result that reports M. tuberculosis (Mtb)detection by a WHO-recommended assay -both rapid molecular assays or mycobacterialculture with subsequent speciation are acceptable as inclusion criteria.
4. Women of childbearing potential (including females <2 years post-menopausal) must havea negative pregnancy test at enrolment.
5. Participants must be willing to have an HIV test done unless there is compellingevidence that the patient is HIV-infected at the time of randomization.

Exclusion Criteria:

1. Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID isindicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
2. People institutionalized (incarceration in jail or prison, or due to chronic mentalillness). If incarcerated during the study, participants may be terminated, thoseincarcerated in the first 8 weeks of follow up will be late exclusions and replaced*.Patients either who are planned to be hospitalized or currently hospitalized whilsttreated for MDR TB in a TB hospital or ward may be enrolled.
3. Receipt of multi-drug TB treatment (including rifamycin plus isoniazid preventivetreatment regimens) for ≥3 days in the 6 months prior to randomization. Participantswho have received ≥3 days of TB preventive treatment in the month prior to TBtreatment initiation will also be excluded.
4. Currently Pregnancy/breastfeeding. Women who conceive and are found to be pregnant inthe first 4 weeks of the trial will be terminated from the trial and excluded from theanalysis.
5. Any of the following laboratory parameters taken prior to randomization:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upperlimit of normal (ULN);
• Total bilirubin > 2 x ULN;
• Neutrophil count ≤ 700 neutrophils /mm3;
• Platelet count < 50,000 cells / mm3
• Haemoglobin concentration less than 8 g/dL
• Serum creatinine concentration more than twice the upper limit of normal

6. Co-treatment in the three months prior to randomization, or planned treatment over thecourse of the trial follow up with any one of the following agents:

• anticoagulant therapy
• immune modulating therapy (cancer treatments, any oral or daily use of inhaledsteroids;
• Antacids or proton pump inhibitors - including self-treatment and prescription

7. History or clinical record of sensitivity, asthma or allergy that could be attributedto NSAIDs
8. Weight < 45kg at baseline.
9. History or clinical record suggestive of any of the following in the past two years:

• peptic ulcer disease or gastro-intestinal bleeding,
• coagulopathy or other bleeding disorder,
• renal disease requiring hospitalization - in addition, any prior record at anytime of acute kidney injury will be an exclusion criterion.
• liver disease requiring further investigation or hospitalization,
• underlying cardiovascular disease or risk factors for cardiovascular disease.

10. Patients with HIV infection (irrespective of ART status) if:

• CD4 <350 cells/mm3
• if on ART, unsuppressed (>200 copies/ml) viral load
• if not on ART, either in the opinion of the attending doctor or according tolocal ART guidelines, the patient should initiate ART during the 8-week initialplacebo or NSAID treatment phase.

11. Alcohol use: potential participant either self-reports or in the investigator'sopinion that the patient drinks more than an average of four units/day over a usualweek or is a binge drinker (men: 5 or more drinks; women: consume 4 or more drinks, inabout 2 hours).
12. Major co-morbid conditions or any other finding which in the opinion of theinvestigator would compromise the protocol compliance or significantly influence theinterpretation of results.