There is a growing group of people who have failed to clear the virus after one or more rounds of interferon-based treatment. Someone who relapses after treatment is referred to as a ‘relapser.’ A ‘relapser’ is defined as someone who achieves a sustained virologic response (SVR) during the course of treatment, but in the three or six month follow up period discovers that the virus is again detectable.
For people who relapse after treatment the variations in dosage and length of interferon-based treatments described below offer a further chance of clearing the virus.
There are two different categories of people who do not achieve SVR. It is important to differentiate between them.
- The first group are nil responders. These people do not show an appreciable decline in HCV RNA during treatment. They can be identified within 12 weeks of starting peg-interferon/ribavirin therapy as after 12 weeks they do not achieve a 2 log reduction from the level at the start of treatment. Continued treatment of these nil responders rarely results in further reductions in viral load. Because of this there is very little point in continuing the treatment.
- The second group are partial responders. These are people who have an early virologic response. Their HCV RNA drops more than 2 logs from the level at the start of treatment within the first 12 weeks, but then slows down or evens out. This group of partial responders have a better chance of responding and achieving SVR during retreatment than nil responders. This group also have some chance of achieving SVR if treatment is extended to 72 weeks.
It is now known that there are a number of factors involved which decrease the chances of clearing the virus.
- Genotype 1
- Failure to respond to treatment by week 12
- A high viral load
- Older age
- Length of infection
- Poor adherence to the treatment drugs
- HIV co-infection
- Immunosuppressant treatment following liver transplantation
For people who have not responded to standard (non-pegylated) interferon therapy without ribavirin there is about a 30% chance of a SVR when they are treated with pegylated interferon and ribavirin. But for those people who have failed to respond to standard (non-pegylated) interferon and ribavirin, the rate of SVR is only 10-20%. For people who have not responded to pegylated interferon and ribavirin the options are more limited.
Ribavirin with Erythropoietin (Epoetin)
Anaemia is the most problematic side effect of taking ribavirin. It can often lead to the need to reduce the dose or abandon treatment altogether. The use of the drug epoetin in conjunction with peg-interferon and high doses of ribavirin has been shown to reduce anaemia. This means that the ribavirin dose does not need to be decreased, which in turn leads to higher SVRs.
In a study examining the effects of high dose ribavirin with epoetin it was found that patients who received high dose ribavirin had a significant increase in SVR over those receiving the standard dose - from 34% to 49%. This increase in SVR was the result of a marked reduction in the incidence of relapse, dropping from about 36% to 9%.
Recent studies have also indicated that high doses of ribavirin with epoetin increases SVR in people with genotype 1.