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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 (AUC(τ)) by 22%-36%. ATV/r did not significantly affect boceprevir exposure, but boceprevir AUC(τ) 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.