Telaprevir Exposure Comparable With or Without Concomitant Antiretroviral Therapy

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SAN DIEGO, CA— The pharmacokinetics across combinations of concomitant telaprevir and efavirenz or atazanavir/ritonavir-based regiments in Hepatitis C (HCV)/HIV co-infected patients were comparable and consistent with those observed historically in HCV mono-infected patients, according to Varun Garg, PhD, from Vertex Pharmaceuticals, Inc., Cambridge, MA, at IDWeek 2012.

Garg and colleagues conducted a Phase 2, randomized, placebo-controlled study of patients treated with combined telaprevir and peginterferon/ribavirin or peginterferon/ribavirin HCV therapy (n=60). The pharmacokinetics of telaprevir in patients on stable, predefined antiretroviral therapy regimens was compared with that of patients not receiving ART. Patients receiving non-ART and atazanavir/ritonavir-based therapy received telaprevir 750mg every eight hours. Patients on efavirenz received telaprevir 1,125mg every eight hours; the higher dose was to compensate for previously-observed interactions in healthy volunteers (47% decrease in telaprevir Cmin).

Researchers performed a non-compartmental analysis on intensive telaprevir concentration-time profiles collected at Week 4. Moreover, predose plasma concentrations of ART medications prior to start of HCV treatment were compared with predose concentrations during treatment to evaluate the effect of telaprevir on efavirenz and atazanavir/ritonavir pharmacokinetics.

Results showed that SVR at 12 weeks post-treatment was achieved in 74% of patients receiving telaprevir and peginterferon/ribavirin and in 45% of patients receiving peginterferon/ribavirin. Among those in the telaprevir and peginterferon/ribavirin arm, SVR rates at 12 weeks were 71% if they did not receive ART, 69% with efavirenz-based therapy, and 80% with atazanavir/ritonavir-based-therapy. In the peginterferon/ribavirin arm, these rates were 33%, 50%, and 50%, respectively.

“There were no HIV breakthroughs,” the investigators reported. Two patients treated with telaprevir and peginterferon/ribavirin experienced HCV RNA breakthrough; one received atazanavir/ritonavir-based-therapy at Week 4, and one received efavirenz-based therapy at Week 12.

In dosing regimens examined in this study, concomitant administration of telaprevir and peginterferon/ribavirin resulted in comparable predose concentrations of ART medication. “The percentage of patients achieving SVR was higher with telaprevir and peginterferon/ribavirin than peginterferon/ribavirin treatment, regardless of ART therapy,” Dr. Garg concluded. “In the efavirenz-based ART group, telaprevir 1,125mg every eight hours provided similar exposure compared to 750mg every eight hours in the atazanavir/ritonavir group."

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