April 3, 2012
Drug interactions are important because they can lead to drug levels that are either too high or too low. In light of these concerns, more drug companies are looking at potential hepatitis C (HCV) drug interactions with HIV medications.
Remember the drug interactions that were reported between the HCV protease inhibitor Victrelis (boceprevir) and HIV drugs? In a previous blog entry, I mentioned that there were some really important drug interactions that led to lower blood levels of Victrelis and lower blood levels of some HIV drugs, such as Reyataz (atazanavir). The same is true for Incivek (telaprevir). There are a lot of drugs that should not be combined with Incivek, such as Kaletra (lopinavir/ritonavir) and Prezista (darunavir, TMC114).
The latest HCV drug in development to be tested for interactions is daclatasvir. I know, the name doesn't exactly roll off your tongue, but it is a promising new drug for HCV treatment. It is a NS5A replication complex inhibitor, which bascially means that it works on a different part of the HCV virus life cycle than protease inhibitors and other HCV medications.
Daclatasvir was studied along with asunaprevir (an HCV protease inhibitor in development) in a small study of HCV-monoinfected patients who previously didn't respond to PEG interferon plus ribavirin. In results presented at CROI 2012, the use of "quad" (four-drug) therapy consisting of daclatasvir plus asunaprevir plus PEG intereferon plus ribavirin led to cures for nine out of 10 patients. In addition, four out of 11 patients who only got the two new HCV drugs (i.e., not PEG interferon or ribavirin) were cured of their HCV infection. Although this is a small study to "test out the waters," these are pretty amazing results. Much larger trials are now planned in HCV-monoinfected patients.
To get ready for future trials in HIV/HCV-coinfected patients, the makers of daclatasvir did three separate studies in healthy volunteers. One study looked at drug interactions between the NRTI Viread (tenofovir) and daclatasvir; another at drug interactions between the NNRTI Sustiva (efavirenz, Stocrin) and daclatasvir; and the last one looked at interactions between daclatasvir and the protease inhibitor Reyataz boosted with Norvir (ritonavir).
The good news here is that daclatasvir doesn't seem to affect levels of Sustiva, boosted Reyataz or Viread. That means that these HIV meds should still work just as well as before.
However, it looks as if the dose of daclatasvir may have to be lower in people taking Reyataz. On the other hand, the dose of daclatasvir may have to be higher in people taking Sustiva.
The next step is to try these new doses of daclatasvir in HIV/HCV-coinfected patients to see if they work well in curing HCV. Let's keep our fingers crossed.