Contributed by Guest Blogger: R. Trenchard ’14
Traditionally, the go-to method used to treat patients with hepatitis C virus has been to administer a combination of antiviral agents called pegylated interferon-a (PEG-IFN) and ribavirin. These agents combat the virus particles that cause HCV, and regulate the immune system. Clinical studies of this type of treatment however, show that the mixture of these two agents achieves the desired sustained virological response (SVR) for only 36%-46% of HCV patients. This sad statistic has led to recent research that has proposed a more advanced treatment method that includes specifically targeted antiviral therapy for HCV (STAT-C). This treatment would work like HIV therapy and involve the inclusion of protease and polymerase inhibitors to the standard HCV antiviral concoction. It is expected to improve treatment outcomes, because every stage of the HCV life cycle could be a target for STAT-C agents.
The STAT-C agents mentioned above have worked in trials because they target enzymes that are essential for viral replication. Currently they have been used in addition to PEG-IFN and ribavirin, but once there are a sufficient amount of STAT-C agents licensed they can be used alone as a combination therapy used to act at distinct stages of viral replication and to create a barrier to resistance. Like HIV therapy however, these drug combinations increase the risk for drug-drug interactions (DDI) in patients. Some of these drug reactions include anaemia, haematological adverse events, and mitochondrial toxicity. Aside from this some patients for whom the treatment works for can suffer from side effects ranging from flu-like symptoms to anemia and cardiovascular problems.
This evokes a number of questions. With such dangerous risks involved, is the treatment worthwhile? What characteristics of HIV and HCV allow them both to be treated with protease and polymerase inhibitors? Can this type of treatment be used on other viruses as well?
If it is indeed expected to improve the outcomes of the treatments, then it should be a simple calculation as to whether or not the risks outweigh the reward; even though there may be heightened risks of complications and drug-drug interactions, the key statistic is how beneficial the drug is in improving the chances of survival in the subjects. Even if it’s high-risk high-reward, patients should be able to at least elect to try the treatment. As we see more and more cases of both successes and failures, we should be able to begin modifying the treatments in an attempt to maximize the good and, however possible, eliminate some of the problematic interactions.