Strengthening Investigation on the Role of HBV Resistance Monitoring

Monitoring drug resistance in HBV is very important. Professor Scott Bowden, from the Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia, presented a report on the role of HBV resistance monitoring. He said that in developed countries, nucleoside and nucleotide analogue inhibitors of the hepatitis B virus (HBV) polymerase/reverse transcriptase (NRTI) were now widely used to treat CHB due to their convenience, safety and efficacy. Unfortunately, because of the unusual replication strategy used by HBV, NRTI are virustatic rather than virucidal. Consequently, in the long-term, development of viral resistance is common and is becoming a major cause of treatment failure. Viral breakthrough associated with selection of antiviral-resistant HBV usually precedes biochemical breakthrough, clinical deterioration and progressive liver failure. NRTI can be classified into subgroups based on structure and because resistance to different classes of NRTI does not usually confer significant cross resistance to other classes, resistance can be managed by switching therapy or continuing therapy by adding additional NRTI.

Professor Bowden pointed out that measurement of viral load was indispensable for monitoring and confirming the presence of NRTI resistant virus, since nearly all instances of resistance to NRTI were initially identified by a sustained rise in viral load that occured despite continuing antiviral therapy. Since factors other than drug resistance (for example, poor patient compliance) can affect viral load, it cannot be automatically assumed that rising loads are indicative of drug resistance, which requires confirmation by other methods. Drug resistant HBV can be detected by genotyping and/or phenotyping, but only the latter provides direct measurements of in vitro resistance to specific drugs. In developing countries the situation is even worse and many obstacles need to be overcome for the therapeutic control of hepatitis B. NRTI use may be unfunded or sub-optimal NRTI therapy may be used because of lack of resources. This may lead to more rapid development of resistant virus which may preclude rescue therapy by more active agents. Economic factors may also delay detection of early resistance because of the inability to monitor HBV DNA levels. Finally, the identification of the pattern of the resistance changes in the HBV polymerase/reverse transcriptase is also important because it indicates the other classes of drugs that may be effective. However, this too requires funding. These problems need to be addressed if we are to reduce the development of resistant virus and to limit its potential transmission.