Boceprevir/PI Interaction: A "Dear Doctor" Letter We Didn't Want to Get

February 10, 2012

Paul E. Sax, M.D.

Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

By now I'm sure that most of you ID folks out there have received the following letter from Merck, the makers of boceprevir:


The purpose of this communication is to inform you of recent pharmacokinetic study results evaluating drug interactions between VICTRELIS, an oral chronic hepatitis C virus (HCV) NS3/4A protease inhibitor, and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors … VICTRELIS reduced mean trough concentrations of ritonavir-boosted atazanavir, lopinavir, and darunavir by 49%, 43%, and 59%, respectively. Merck does not recommend the coadministration of VICTRELIS and ritonavir-boosted HIV protease inhibitors.

Boceprevir levels were also substantially lowered by lopinavir/r and darunavir/r.

Yes, we already knew that the telaprevir-boosted PI interactions were tricky. It's basically atazanavir/ritonavir, no other options.

(Outside of the boosted PIs, you can use raltegravir or efavirenz with telaprevir, but the latter requires, 1125 mg three times/day, upping the cost by 50%. Gasp.)

The reason this "Dear Doctor" letter was so disappointing was that boceprevir was supposed to be easier in this regard. In this study presented at IDSA of peg/ribavirin + boceprevir for co-infected patients, all boosted PIs were allowed, only NNRTIs excluded. But that study was small (n=64), and in hindsight perhaps the slower-than-expected HCV RNA reduction had a pharmacokinetic explanation.

For now, the bottom line is that there really is no optimal HCV protease inhibitor for HIV/HCV co-infected patients, especially for those on a boosted PI.

And why careful assessment of those with HIV/HCV is critical, as many patients are stable enough to wait for the next wave of HCV drugs.

Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.

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NEJM Journal Watch is a publication of the Massachusetts Medical Society.
See Also
FDA Drug Safety Communication: Important Drug Interactions Between Victrelis (Boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV) Protease Inhibitor Drugs

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