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HCV viral load and new treatments for the hepatitis C virus

Pictogramme horloge Dominique Brunengo Pictogramme horloge July 2015

Hepatitis C treatment has significantly progressed in recent years thanks to better understanding of the virus’ replication cycle. Treatment is currently based on the use of direct acting antivirals (DAA’s) targeting HCV viral proteins. A marketing authorisation has just been obtained for several DAA’s targeting the hepatitis C virus and there has been major progress in the clinical development of several others. Thus, the standard treatment in 2015 is based on a combination of direct acting antivirals (ofosbuvir, imeprevir, aclatasvir). Simeprevir and daclatasvir belong to the anti-protease group, sofosbuvir belongs to the anti-polymerases.

  • Simeprevir: NS3/4A anti-protease
  • Daclatasvir: NS5A anti-protease
  • Sofosbuvir: NS5B anti-polymerase

These drugs should be prescribed for periods of 12 to 24 weeks according to whether or not they are in combination (sofosbuvir +daclatasvir or sofosbuvir + simeprevir) with ribavirin. The HCV genotype (and its sub-types) is also a factor in determining the form of treatment. Note that the current cost of treatment is very high (€50,000-60,000 for a 12-week combination treatment) and at present is reserved for patients with fibrosis and cirrhosis (F2, F3 or F4 according to Metavir score). The next step will to apply this treatment to patients infected with genotype 3 (the most difficult to eradicate).

The assay of the viral genome is performed,

  • just before commencing treatment,
  • to monitor therapeutic efficacy by means of viral load (VL) kinetics using real-time PCR.

Throughout treatment and a long time thereafter, the same test should be used to ensure coherent results over time, especially when viral load falls to around the quantification/detection threshold. Evaluating viral load at least every 4 weeks during treatment enables verification of compliance and therapeutic efficacy. To ensure full viral elimination, viral load should be measured by quantitative PCR in real-time, 12 and 48 weeks after discontinuing treatment. The absence of viral replication 3 months after discontinuing treatment is a sign of healing. Patients in whom viral load is not detectable at the end of treatment present a very low risk of virological relapse (< 10%). A sustained viral response of 12 weeks is therefore the correct treatment efficacy criteria. Moreover, if the HCV RNA is still not detectable 48 weeks after discontinuing treatment, eradication may be considered as definitive; subsequent monitoring is not necessary except in the case of cirrhotic patients or those presenting liver-related complications.

Information on viral load at the end of treatment is needed to differentiate virological escape from post-therapeutic virological relapse. Some patients have a detectable but non-quantifiable viral load or a load which remains difficult to quantify at the end of treatment. These results should not lead to the antiviral treatment being extended beyond the initially scheduled duration and are not indicative of treatment failure.

However, in some special situations (especially patients with HCV risk factors), viral load will be followed up more frequently (at least annually or in case of abnormal liver assessment) even after a sustained virological response. The objectives of treatment are to eradicate HCV, assuming that the reduced cost of current treatments enable treating a larger patient population, with a dose of only one tablet and over a shorter period than currently proposed.

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