Hepatitis B virus (HBV) is a partially double stranded DNA virus belonging to the Hepadnaviridae Family (Columbia web page, 1998). Hepatitis B is transmitted by blood and blood products as well as sexual intercourse and is prevalent in developing regions of the world. Chronic hepatitis is transmitted vertically from mother to child during pregnancy and is the leading cause of cancer death in the world, affecting 300 million people in the world. ((Lau et al., 2000). There is no known cure and treatments such as interferon alpha have had success only in a restricted number of cases (immunocompetent patients). Therefore it is paramount to focus on new forms of treatment for preventing cirrhosis and liver damage. Recently, new antiviral agents such as lamivudine have shown early signs of promise in clinical trials. However, HBV viral mutations have challenged the long-term use of lamivudine as a therapeutic agent and more clinical trials are needed.

Lamivudine Composition and Function:

Lamivudine is non-toxic cytosine base analogue used in the treatment of Hepatitis B (Johnson et al., 1999). In the last 5 years, this antiviral agent has demonstrated its potent inhibitory activity towards HBV RNA-dependant DNA polymerase (Chau-Ting et al., 2000). Lamivudine when activated suppressed reverse transcription of the HBV DNA polymerase and that ceased viral protein product (Santantonio et al., 2000). Moreover, the HBV-DNA concentration was lowered in serum and so was the number of hepatitis B antigens circulating in the bloodstream (Lau et al., 2000). Lamivudine actively attached to the RNA-DNA dependent polymerase, and inhibited the polymerases normal activity.

Acquired Drug Resistance:

Continued use of lamivudine in treating chronic hepatitis B led to drug resistance, in terms of new strains of HBV. Furthermore, it lead to amino acid mutations : specifically, mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of DNA polymerase of HBV (Chau-Ting et al., 2000). During clinical trials, all the research noted that at least a certain percentage of their subjects had the mutations in YMDD motif. However, not all the mutations proved to be associated with proliferation of virus DNA (Santantoio et al., 2000). The HBV acquired resistance as it sees lamivudine as a threat to its only goal: replication and proliferation of its genome. It can be said that HBV (like many other viruses) is an excellent molecular biologist as it alters its genetic makeup to overcome barriers (lamivudine) that thwart its replication

Combined Treatment:

Dienstag et al., believed that in order to lower drug resistance, a multi-therapeutic combination of drugs should be devised. The combination of drugs, such as antiviral agents could minimize the number of drug resistant HBV strains. This is the combined therapy decreases the overall probability of a mutant HBV strain replicating. This drug-combination therapy is currently being used in the treatment of HIV. In addition to drug resistance, the virus is always one step ahead of the immune system, as it eludes the immune response by altering its genome. In other words, each time the immune system makes antibodies against one strain, the virus has mutated in another. The long-term therapy using lamivudine is still uncertain (Villeneuve et al., 1999). Further experiments on the toxicity and prolonged use of lamivudine are necessary to determine its potential as a treatment in chronic hepatitis B (Lau et al., 2000) Furthermore, combined drug therapy could prove beneficial but costly.

In conclusion, lamivudine was successful in early trials in suppressing and substaintiating HBV replication. The long-term outcome of using lamivudine in curing chronic hepatitis B is unclear (Villeneuve et al., 1999). Moreover, the safety and long-term use of this antiviral agent are not known and must be considered if this treatment is to become mainstream. Perhaps the combination of antiviral drugs will yield better results, as they decrease the likelihood of a mutant strain dodging these drugs.