Lecture: Direct Acting Antivirals (DAA)

Direct Acting Antivirals (DAA) represents a major breakthrough in the treatment of chronic hepatitis C (HCV) infection.  Although more than fifty new therapeutic agents are in the pipeline, two are expected to be FDA approved later in this calendar year- bocepravir and telapravir.  This lecture aimed to define the populations who benefit most from the addition of one of these agents to the standard dual regimen of peginterferon and ribavirin; furthermore, the response-based treatment algorithm was discussed.

It is critical to recognize that both agents are to be used in genotype 1 infection.  The ideal patient is either treatment naive, or has previously experienced a response-relapse to standard of care; in these situations, the SVR rate of therapy is roughly 80%.  This remarkable response rate is tempered somewhat (to the 60-65% range) for previous incomplete-responders (ie. those who may have dropped 1 or 2 log on treatment but were never viral load undetectable).  Previous null-responders can expect a SVR in the 30% range.

The idea behind these new agents are that they work directly on the virus, and not with the body’s innate interferon mechanism.  Therefore, for patients with inadequate responses to the interferon portion of treatment, drug resistance can be anticipated; if patients have detectable viral loads at weeks 4, 8 and 12, even this new regimen will not work.

Side effects for these new drugs must also be understood.  For bocepravir, anemia is more severe.  You should not treat the anemia by reducing the dose of the DAA! Alternative considerations include adding an erythropoeitin agent or reducing the dose of ribavirin.  Secondly, a metallic taste in the mouth can be anticipated.  For telapravir, anemia is again seen more frequently, along with development of anal symptoms, including pain or pruritus.  Rash is also more common, and is a steroid-responsive excematous reaction.

In sum, these new DAA agents will vastly increase the pool of potential treatment candidates.  For a closer look at some of the details of one of the recently published studies, refer to this link-

http://www.nejm.org/doi/full/10.1056/NEJMoa0908014

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