Paul E. Sax, MD

Disclosures

March 29, 2012

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Hi. This is Paul Sax from Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts. Today, I'd like to discuss some of the presentations and posters from this year's CROI (19th Conference on Retroviruses and Opportunistic Infections) that dealt with hepatitis C virus infection (HCV), one of the most exciting areas in infectious disease right now.

The first 2 studies are telaprevir and boceprevir studies.[1,2] In both studies, the drugs were added to standard interferon plus ribavirin in HIV/HCV-coinfected patients with genotype 1 infection. The good news is that in both of these studies, the sustained virologic responses at week 12 looked excellent, substantially better than with interferon/ribavirin alone and almost as good as in studies of monoinfected patients.

Giving these 2 drugs to patients with HIV is challenging, in part because of the significant drug interactions between the HCV protease inhibitors that are available now. We saw at CROI the full results of the boceprevir-boosted protease inhibitor drug interaction study.[3] The bottom line is that boceprevir substantially lowers the levels of HIV protease inhibitors and vice versa; for lopinavir and darunavir, at least, levels of boceprevir are substantially lowered, too. For now, I would say that we should not coadminister those drugs, even though in the small study I just mentioned, coadministration did not appear to have an effect on response. But again, the results were from a small study.

Another drug interaction study of note looked at the TMC435 HCV protease inhibitor given with a variety of HIV medications.[4] TMC435 is a substrate of CYP3A4 and, not surprisingly, it did not have any interaction with raltegravir. Encouragingly, it did not have an interaction with rilpivirine or tenofovir, but it did have a substantial interaction with efavirenz, causing levels of TMC435 to be substantially lowered.

Daclatasvir is not an HCV protease inhibitor; it is an NS5A inhibitor. It was tested with tenofovir, with efavirenz, and with atazanavir and ritonavir.[5] There was no significant interaction with tenofovir, but efavirenz did lower the levels of daclatasvir, whereas atazanavir and ritonavir seemed to increase them. However, unlike the boceprevir study I mentioned and the TMC435 study, it does appear that dose adjustments of the daclatasvir will be possible when coadministered with these HIV drugs.

The last study I want to mention is not about drug interactions, but about interferon-free regimens. The exciting nucleotide 7977 has shown excellent activity in HCV monoinfected patients, especially in patients with with genotype 2 and 3, where a small study found that 12 weeks of 7977 plus ribavirin has led to incredible cure rates.[6] Here, we saw the results in HCV genotype 1 null responders,[7] people who had not responded to interferon/ribavirin alone; the results were quite interesting. The viral kinetics were excellent. The viral load dropped very quickly; it seemed to drop just as quickly as in people who had responded to interferon/ribavirin, but then after stopping at week 12, virtually all the patients who were treated relapsed. What this tells us is that these null responders -- who are very difficult to treat, have a high body mass index (BMI), have an unfavorable IL-28B genotype, and have other factors that make them less likely to be cured -- will need to be treated with this combination either for a longer period or, perhaps, with another drug added. I personally am still very excited about this combination in treatment-naive patients with genotype 1. We already knew these null responding genotype 1 patients were very difficult to treat.

That is a quick summary of some of the more exciting presentations on HCV from the Retrovirus Conference. You can see the links to these presentations or posters at the references at the bottom or on my blog, HIV and ID Observations.

Thank you very much for listening.

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