Atazanavir/Ritonavir versus Boceprevir
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Study Design
In a pharmacokinetic (PK) study in healthy volunteers, coadministration of boceprevir (BOC) and ritonavir-boosted atazanavir (ATV/r) resulted in reduced exposures of ATV.1,2 Geometric mean ratios (GMRs; ATV/r + BOC / ATV/r) [90% CI] of AUC, Cmax, and Cmin were 0.65 [0.55, 0.78], 0.75 [0.64, 0.88], and 0.51 [0.44,0.61], respectively. BOC exposure was not affected by administration with ritonavir-boosted atazanavir; GMRs (BOC + ATV/r / BOC) [90% CI] of AUC, Cmax, and Cmin were 0.93 [0.80,1.08], 0.95 [0.87,1.05], and 0.82 [0.68,0.98], respectively.
In a separate multi-center, open-label phase II trial, HIV/HCV coinfected patients also showed consistent results with the study conducted in healthy subjects; coadministration of BOC and ATV/r resulted in reduced exposures of ATV.3 7 patients were on treatment with ATV/r (300/100 mg once daily) with nucleoside reverse-transcriptase inhibitors (NRTI) backbone (tenofovir (TDF) and emtricitabine (FTC)/ lamivudine (3TC)) and were well suppressed on antiretroviral therapy (ART; HIV viral load < 50 cp/mL). For hepatitis C treatment, patients received peg-IFN2b (1.5 µg/kg/week) + ribavirin (RBV; 800 to1400 mg/d) + BOC (800 mg three times daily) after coadministration of peg-IFN 2a (1.5 µg/kg/week) and RBV (1000mg/day (<75Kg) or 100mg/day (>75Kg)) in 4-week lead-in phase. Pharmacokinetic (PK) parameters, Cmax and AUC, were determined at baseline and after 4 weeks of BOC.
Study Results
Coadministration with BOC resulted in 50.5% decrease in exposure (AUC) and 54% decrease in plasma concentration (Cmax) of ATV (p=0.01). When compared with historical data (Kanter et al study (JAC 2013) performed in healthy volunteers who administered BOC without ARV), BOC AUC, Cmax and Ctrough were 0.78 [0.87,1.05], 0.74 [0.68, 0.98] and 1.87 [0.80, 1.08], respectively.
Study Conclusions
Concomitant use of boceprevir and ritonavir-boosted atazanavir is not recommended.1,2,4 If BOC was initiated for treatment of chronic HCV infection in a patient coinfected with HIV who is receiving a suppressive antiretroviral regimen containing ATV/r, the patient should be closely monitored for HCV treatment response and potential HCV and HIV virologic rebound.
References
Hulskotte E, Feng HP, Xuan F, van Zutven MG, Treitel MA, Hughes EA, Butterton JR. Pharmacokinetic interactions between the hepatitis c virus protease inhibitor boceprevir and ritonavir-boosted hiv-1 protease inhibitors atazanavir, darunavir, and lopinavir. Clinical Infectious Diseases. 2012; 5: 718-726.
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