Figure 1

Diagram showing the timings of clinical trial visits and study regimens to tuberculosis (TB) treatment. Patients were screened after 5 weeks of standard TB chemotherapy administered as a fixed dose combination (Rmp – rifampicin, Inh – isoniazid, Pza – pyrazinamide, Emb – ethambutol). If patients met all eligibility criteria they were enrolled after 6 weeks of TB chemotherapy and switched to rifabutin 300 mg daily in place of rifampicin. At the end of the intensive phase (8 weeks of TB treatment) they continued with rifabutin 300 mg daily and isoniazid 300 mg daily. This was followed by the first pharmacokinetic visit (PK1) at which the bioavailability of rifabutin in the absence of LPV/r was assessed. The patients then initiated antiretroviral therapy (ART) and altered their dose of rifabutin based on the randomization to either 150 mg tiw of 150 mg daily. After a month of ART a second pharmacokinetic evaluation (PK2) was completed. Patients then switched doses of rifabutin from 150 mg tiw to daily, or vice versa, and after a further month of treatment a third pharmacokinetic evaluation was completed (PK3). Patients then continued with rifabutin at the dose they were on at PK3, in combination with ART and isoniazid until a total of 24 weeks of TB treatment had been completed. Patients continued ART after stopping TB treatment.