Pharmacokinetic Interactions Between the Hepatitis C Virus Protease Inhibitor Boceprevir and Ritonavir-Boosted HIV-1 Protease Inhibitors Atazanavir, Darunavir, and Lopinavir

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Abstract
Background. Boceprevir represents a new treatment option for hepatitis C (HCV)–infected patients, including those with HCV/human immunodeficiency virus coinfection; however, little is known about pharmacokinetic interactions between boceprevir and antiretroviral drugs. Methods. A randomized, open-label study to assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted protease inhibitors (PI/r) was conducted in 39 healthy adults. Subjects received boceprevir (800 mg, 3 times daily) for 6 days and then received PI/r as follows: atazanavir (ATV) 300 mg once daily, lopinavir (LPV) 400 mg twice daily, or darunavir (DRV) 600 mg twice daily, each with ritonavir (RTV) 100 mg on days 10–31, plus concomitant boceprevir on days 25–31. Results. Boceprevir decreased the exposure of all PI/r, with area under the concentration–time curve [AUC] from time 0 to the time of the last measurable sample geometric mean ratios of 0.65 (90% confidence interval [CI], .55–.78) for ATV/r; 0.66 (90% CI, .60–.72) for LPV/r, and 0.56 (90% CI, .51–.61) for DRV/r. Coadministration with boceprevir decreased RTV AUC during a dosing interval τ (AUCτ) by 22%–36%. ATV/r did not significantly affect boceprevir exposure, but boceprevir AUCτ was reduced by 45% and 32% when coadministered with LPV/r and DRV/r, respectively. Overall, treatments were well tolerated with no unexpected adverse events. Conclusions. Concomitant administration of boceprevir with PI/r resulted in reduced exposures of PI and boceprevir. These drug–drug interactions may reduce the effectiveness of PI/r and/or boceprevir when coadministered.

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