Pharmacokinetics of rifabutin during atazanavir/ritonavir co-administration in HIV-infected TB patients

Abstract Background & objective Rifabutin (RBT) is the rifamycin that is recommended to treat tuberculosis (TB) in HIV-infected individuals during combination antiretroviral therapy (ART) containing HIV protease inhibitors (PIs). We studied the pharmacokinetics of rifabutin at doses of 300 mg thrice weekly and 150 mg daily during concomitant atazanavir/ritonavir (ATZ/r) administration in adult HIV-infected TB patients treated in the Revised National TB Control Programme (RNTCP) in India. Methods This was a multi-centric study conducted in 45 adult HIV-infected TB patients, who were being treated for TB with a RBT-containing regimen and an antiretroviral treatment regimen with ATZ/r, at doses of 300 mg thrice-weekly (n = 36) or 150 mg daily (n = 9). Serial blood draws at pre-dosing and at 1, 2, 4, 6, 8, 12 and 24 hours after drug administration were done. Plasma RBT was estimated by high pressure liquid chromatography (HPLC). Results The peak concentration (C max ) of both doses were within the therapeutic range (0.45–0.90 μg/ml) of RBT. Proportion of patients having C max above or below the therapeutic range and trough concentration (C min ) below the minimum inhibitory concentration of RBT did not significantly differ between the two doses. TB treatment outcomes were also similar at both doses. Conclusions This is the first and only study from India reporting on the pharmacokinetics of RBT at 300 mg thrice weekly and 150 mg daily doses. Both doses yielded similar plasma RBT concentrations, outcomes and were well tolerated. RBT can be administered at either doses during ATZ/r co-administration in HIV-infected patients with TB.