Intervention
Participants were randomized to 1 of 3 treatment arms (1.4:1:1). Proportionally more participants were randomized to arm 1 to account for anticipated higher mortality with standard of care compared with the intervention arms. Treatment arms were as follows: arm 1 (standard of care): rifampicin 10 mg/kg, isoniazid (H) 5 mg/kg, ethambutol (E) 15 mg/kg, and pyrazinamide (Z) 25 mg/kg daily for 56 days; arm 2: as per arm 1 plus adjunctive 25 mg/kg rifampicin (total dose, 35 mg/kg) and linezolid (1200 mg for 28 days, reducing to 600 mg for 28 days) daily for 56 days; and arm 3: as per arm 2 plus adjunctive aspirin (1000 mg) daily for 56 days.Dosing was calculated by weight bands, published elsewhere [Participants allocated to arms 2 and 3 were further randomized (1:1) to receive oral rifampicin 35 mg/kg or IV rifampicin 20 mg/kg daily for the first 3 days of therapy (in addition to HZE and linezolid ± aspirin, according to the experimental arm). Results of this PK substudy are published elsewhere [All participants in the LASER-TBM trial not on antiretroviral therapy (ART) were referred to local government clinics to initiate ART according to the Western Cape Consolidated Guidelines for HIV Treatment. Given the potential interaction between rifampicin and lopinavir/ritonavir and between dolutegravir, clinics were advised to double doses of these drugs until 2 weeks after anti-TB treatment had ceased.