Special Report - Emerging Viruses

Virgil: virus resistance watch

Cross-section of an HIV-1 infected lymphocyte. ©Inserm/Institut Pasteur Cross-section of an HIV-1 infected lymphocyte.
©Inserm/Institut Pasteur

With a € 9 million, four-year grant from the European Commission, 70 laboratories from 16 Member States in the Virgil network (1) have joined forces to develop multi-therapy strategies to combat antiviral drug resistance in hepatitis B and C and influenza patients. They are also developing responses to the risk of new pandemics. Research*eu interviewed Virgil’s coordinator, Fabien Zoulim from Inserm (FR).

How did antiviral drug resistance come to people’s attention?

Awareness started with the Aids epidemic. For the first time ever, a chronic viral disease could benefit from long-term antiviral drug treatment. We knew about hepatitis B and C, which at that time we called “non-A non-B”, but we had no drugs as yet to treat them. With AIDS on the other hand, one of the first antiviral drugs, AZT, started being used in the mid-eighties. Here we quickly recognised that, after a short improvement in a patient’s condition, a relapse followed as the virus became resistant to AZT. We then combined AZT with one, then two, and even three other antiviral drugs, culminating in the present tritherapy which has considerably improved patients’ life expectancy.

Can the experience gained with AIDS be applied to other viral diseases?

Yes, and particularly hepatitis. Remember that 15 million Europeans are infected by hepatitis B and C viruses and that chronic hepatitis is responsible for two-thirds of all cirrhoses and cancers of the liver. Thanks to experience with HIV, we have progressively introduced multi-therapy strategies in our fight against hepatitis, combining several drugs to reduce the development of any resistances. These strategies now allow us to cure – and here I mean to completely eradicate the virus from the patient’s body – 50 % of hepatitis C cases. On the other hand, multi-therapy treatment can only halt hepatitis B, not cure it. This is why vaccination is so important.

What about the 50 % of hepatitis C patients who cannot be cured by bitherapy?

This is one of the topics that Virgil is researching. We are working on two approaches. The first concentrates on the patient, investigating the immunological reasons for therapy failure. The second focuses on the virus, where we know that certain genotypes are more resistant to treatment. In short, we are aiming to integrate the issue of viral resistance right from the drug design stage. Every time a new substance is developed, scientists first test it on the hepatitis C virus’s replication systems in cell cultures. Any resistant strains appearing are characterised genetically and pharmacologically by testing their sensitivity to other antiviral drugs. In this way we are able to anticipate viral resistance problems at a very early stage in new drug development.

Do you have the same resistance problems with flu?

No, here the problem is different. In terms of public health, the flu problem is the danger of a massive pandemic like we saw with Spanish flu following the First World War. If such a pandemic were to strike, the necessary vaccines would arrive too late and antiviral drugs would have to be prescribed on a massive scale. Virgil’s work is to anticipate the resistances which would inevitably occur in such a case. A European surveillance network is therefore collecting different strains of flu viruses in circulation and testing their resistance to antiviral drugs. The intention is that, should a pandemic ever threaten, we will already have a base of reference data on the sensitivity of flu viruses to a range of antiviral drugs. This can only be good for public health.

Mikhail Stein

  1. Vigilance against viral resistance.

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To find out more

  • Virgil – 12 partners (BE - DE - CH - DK - ES - FR - IE - IT - PT - UK - USA) and various international organisations
  • www.virgil-net.org/