Pharmacokinetics of different rifabutin dosing strategies with lopinavir/ritonavir-based ART
Polly Clayden, HIV i-Base
Interactions between rifampicin and protease inhibitors makes treating patients coinfected with HIV and TB more complicated.
Rifabutin is an alternative rifamycin, which can be used in patients receiving a protease inhibitor. Recent findings suggest that the current recommended dose of lopinavir/r (LPV/r) is suboptimal. There are limited data regarding the newer formulation of LPV/r.
Investigators from University of Cape Town, International Union Against Tuberculosis and Lung Disease and WHO evaluated the pharmacokinetics (PK) of rifabutin in co -infected patients on a first line TB regimen before and after the initiation of LPV/r-based ART.
Suhashni Naiker and colleagues showed findings from this study in a poster at CROI 2011.
A group of 16 patients on stable rifabutin-containing TB regimens were initiated on LPV/r-containing HAART. At HAART initiation they were randomised to receive either: rifabutin 150 mg daily for 1 month followed by 150 mg 3 times weekly, or 3 times weekly doses followed by daily doses.
The investigators measured serial rifabutin and 25-O-desacetyl rifabutin concentrations during a dose interval after 4 weeks of rifabutin 300 mg daily, after 4 weeks of 150 mg rifabutin daily with LPV/r-based HAART, and after 4 weeks of rifabutin 150 mg 3 times a week with LPV/r-based ART.
At baseline the participants were a mean (SD) of 31.6 (5.5) years, 59.0 (9.4) kg, 160.1 (7.1) cm and 147 (43) CD4 cells/mm3. Ten were men. Two were not included in the analysis due to poor adherence.
The investigators reported median AUC0-24 and Cmax, for participants receiving 300 mg rifabutin daily, 150 mg rifabutin three times a week, and 150 mg rifabutin daily, respectively, of 3026 ng/mL.h and 297ng/mL, 2307 ng/mL.h and 168 ng/mL, and 5010 ng/mL.h and 311ng/mL.
They found that rifabutin was well tolerated at all dosing strategies. There was one case of uveitis that occurred before LPV/r was initiated, and one grade 2 transaminitis and one grade 2 neutropenia were also reported.
They concluded that rifabutin 150 mg daily used with LPV/r produces Cmax concentrations within the recommended target range of 300 to 900 ng/mL.
Naiker S et al. Pharmacokinetic evaluation of different rifabutin dosing strategies in African TB patients on lopinavir/ritonavir-based ART. 18th CROI, 27 February–2 March 2011, Boston. Poster abstract 650.