Intervention: Pravastatin
Trial phase: Phase 2
ATC code: C10AA03 | C10BA03 | C10BA11 | C10BA12 | C10BX02
SMILES: [H][C@@]12C(=C[C@@H](O)C[C@@H]1OC(=O)[C@@H](C)CC)C=C[C@H](C)[C@@H]2CC[C@@H](O)C[C@@H](O)CC(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 6
Group description: Pravastatin 80 mg, isoniazid 300 mg, rifampin 450 mg (weight <50 kg) or 600 mg (weight >50 kg), pyrazinamide 20-25 mg/kg, and ethambutol 15-20 mg/kg daily for 14 days Arm 2 will only be recruited if pravastatin 40 mg is well tolerated and safe, yet drug exposures are significantly reduced due to the known interaction with rifampin.

Pravastatin: Phase IIB clinical trial: A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.

A two-week safety/PK study to determine pravastatin exposures over 24 hours when given together with first-line treatment (HRZE) and ensure the combination is safe and well-tolerated.
Eligibility criteria:
Inclusion Criteria:

18 years of age or older
Clinical signs and symptoms of pulmonary tuberculosis
Abnormal chest radiograph consistent with pulmonary tuberculosis
At least one sputum positive for M. tuberculosis by Xpert Mycobacterium tuberculosis (MTB)/resistance to rifampicin (RIF) with a cycle threshold (Ct) <28.
Documentation of HIV status
Weight ≥45 kg
Karnofsky score of at least 60
Ability to provide informed consent
Ability to adhere to study follow-up visits
Ability to adhere to contraceptive requirements and willing to use two forms of contraception.
Five days or fewer of anti-tuberculosis treatment within the previous 3 months

Exclusion Criteria:

A history of severe adverse reactions to any statin or any other study agent or contraindications to use of statins.
Current use of statins or other lipid-lower agents;
Clinical indication for statin therapy based on cardiovascular risk (Familial hypercholesterolemia, Previous history of myocardial infarction or stroke)
For HIV-positive individuals, a cluster of differentiation 4 (CD4+) T-cell count <100/mm3
Use of antiretroviral drugs
Hemoglobin concentration less than 7 g/dL;
Baseline creatinine kinase elevation more than three times the upper limit of normal
Abnormal baseline laboratory values (Baseline alanine aminotransferase (ALT) concentration more than three times the upper limit of normal, Serum creatinine concentration more than twice the upper limit of normal, Serum total bilirubin level greater than twice the upper limit of normal, Platelet count < 100,000/mm3, White Blood Cell (WBC) < 2500 (mcL))
Pregnant or breastfeeding;
Silico-tuberculosis.
Currently receiving TB treatment
Concomitant disorders or conditions for which isoniazid, rifampin, pyrazinamide, or ethambutol is contraindicated. These include sever hepatic damage, acute liver disease of any cause, acute uncontrolled gouty arthritis and peripheral neuropathy.
Any medical or psychological condition which, in the view of the study investigator, makes study participation inadvisable.
Infection with an isolate known to be resistant to a first -line TB drug; for example rifampin.
More than five days of anti-tuberculosis treatment within the previous 3 months
Planned or current use of cyclosporine, tacrolimus, erythromycin or colchicine
Central nervous system (CNS) TB
Extra-pulmonary TB only, not in combination with pulmonary TB
History of TB